Disease / physique analysis method, disease / physique analysis system, program, and computer-readable recording medium

Abstract

The present invention relates to a method for analyzing a disease / physique, a system for analyzing a disease / physique, a program, and a computer-readable recording medium. Provided is a disease / physique analysis method with which it is possible to analyze the onset risk of a disease such as a lifestyle disease using a sample collected by a simple method. The analysis method comprises: an extraction step for extracting RNA from a sample collected by a non-invasive means; a step for quantifying mRNA associated with the onset of a specific disease and / or a specific constitution among the mRNA present in the RNA; and an analysis step for analyzing the state of the specific disease and / or the specific body constitution on the basis of the quantified amount of mRNA.

Description

[0001] This application is a divisional application of the Chinese invention patent application with application number 201910794931.6, application date August 27, 2019, and invention name "Disease / Constitution Analysis Method, Disease / Constitution Analysis System, Program and Computer-readable Recording Medium". Technical Field

[0002] The present invention relates to a disease / physique analysis method, a disease / physique analysis system, a program, and a computer-readable recording medium. Background Art

[0003] Lifestyle diseases refer to "a group of diseases related to lifestyle habits such as eating habits, exercise habits, rest, smoking, and drinking and their onset and progression." Examples include non-insulin-dependent diabetes, obesity, hyperlipidemia (excluding familial hyperlipidemia), hyperuricemia, circulatory system diseases (excluding congenital circulatory system diseases), colorectal cancer (excluding familial colorectal cancer), and periodontal disease. In addition, the prevention of lifestyle diseases has become an urgent issue. Therefore, it is also important to examine the risk of lifestyle diseases before they occur.

[0004] As a test for predicting the risk of lifestyle diseases, a method of measuring the concentration of amino acids in the blood can be cited (for example, refer to Patent Document 1). In this test, the state of the index of lifestyle diseases is evaluated according to a predetermined standard using the concentration of amino acids in the blood.

[0005] Prior art literature

[0006] Patent Literature

[0007] Patent Document 1: International Publication No. 2014 / 168125 Summary of the invention

[0008] Problems to be solved by the invention

[0009] However, this test uses blood and is not a non-invasive test that does not impose a burden on the living body.

[0010] Therefore, as a test that can be easily collected, research has been conducted on tests using genes. Here, as genetic tests, there are DNA tests and RNA tests, but DNA is a gene that does not change throughout life, and even if DNA with a high risk of developing a disease is present, it does not necessarily mean that the disease will occur.

[0011] On the other hand, RNA testing is a test that analyzes the risk of developing lifestyle diseases due to acquired factors at the genetic level. It is considered suitable for testing the risk of developing lifestyle diseases caused by gene mutations due to acquired factors such as lifestyle, environment, stress, and aging.

[0012] In addition, if RNA tests can examine acquired causes, it is possible to understand the state of the body at different stages, and it is possible to improve the state through lifestyle, environment, diet, supplement intake, etc., and prevent the onset of diseases before they occur.

[0013] An object of the present invention is to provide a disease / constitution analysis method, a disease / constitution analysis system, a program, and a computer-readable recording medium that can analyze the risk of developing a disease such as a lifestyle disease using a sample collected by a simple method.

[0014] Methods used to solve problems

[0015] The present inventors have conducted intensive studies to solve the above problems and, as a result, have found that the above objects can be achieved by using samples collected by non-invasive means, thereby completing the present invention.

[0016] That is, according to the present invention, the following solutions can be provided.

[0017] (1) A disease / physique analysis method, comprising: an extraction step of extracting RNA from a sample collected by non-invasive means; a step of quantifying mRNA present in the RNA that is associated with the onset of a specific disease and / or a specific physical condition; and an analysis step of analyzing the state of the specific disease and / or the specific physical condition based on the quantified mRNA amount.

[0018] (2) The disease / physique analysis method according to (1), wherein the sample is saliva or oral mucosa.

[0019] (3) A method for analyzing a disease / physique as described in (1) or (2), wherein the specific disease is at least one of cancer, arteriosclerosis, cerebral infarction, myocardial infarction, immune function-related diseases, autoimmune diseases, type I diabetes, type II diabetes, hyperlipidemia, thrombosis, bulimia, sweets intake, obesity, metabolic syndrome, cholesterol-related diseases, neutral fat-related diseases, cirrhosis, kidney stones, cholelithiasis, urolithiasis, emphysema, nicotine dependence, bone disease, inflammation, rheumatoid arthritis, arthritis, gout, low back pain, duodenal ulcer, anemia, rhinitis, restless legs syndrome, cluster headache, migraine, age-related macular degeneration, glaucoma, astigmatism, skin aging, atopy, sun spots, freckles, fatigue, chronic fatigue, and alopecia areata, and the specific constitution is detoxification, drug resistance, alcohol metabolism, caffeine metabolism, exercise therapy, sleep time, and longevity.

[0020] (4) A disease / constitution analysis system, comprising a measuring device and an analyzing device, wherein the measuring device comprises: a measuring unit for quantifying the amount of mRNA related to the onset of a specific disease and / or a specific constitution in RNA extracted from a sample collected by non-invasive means; and a sending unit for sending the amount of mRNA quantified by the measuring unit to the analyzing device, wherein the analyzing device comprises: a receiving unit for receiving the amount of mRNA sent from the measuring device; and an analyzing unit for analyzing the state of the specific disease and / or the specific constitution based on the amount of mRNA.

[0021] (5) A program for causing a computer to function as the following units, wherein the units are: a unit for obtaining data on the amount of mRNA obtained by quantifying mRNA related to the onset of a specific disease and / or a specific physical constitution in RNA extracted from a sample collected using a non-invasive method; and a unit for analyzing the status of the above-mentioned specific disease and / or the above-mentioned specific physical constitution based on the above-mentioned mRNA amount data related to the onset of the above-mentioned specific disease and / or the above-mentioned specific physical constitution.

[0022] (6) A computer-readable recording medium having a program for causing a computer to function as: a unit for obtaining data on the amount of mRNA obtained by quantifying mRNA associated with the onset of a specific disease and / or a specific constitution in RNA extracted from a sample collected using a non-invasive method; and a unit for analyzing the state of the specific disease and / or the specific constitution based on the data on the amount of mRNA associated with the onset of the specific disease and / or the specific constitution.

[0023] (7) A method for analyzing a disease / physique, comprising: extracting exosomes from a sample collected by non-invasive means; and detecting miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205, miR-214, let-7a, miR-1229, miR-1246, miR-150, miR-223, A step of quantifying at least one of miR-23a, miR-4644, miR-3976, miR-4306, miR-17-5p, miR-19a, miR-146a, miR-718, miR-375, miR-1290, miR-101, miR-373, miR-320, and miR-574-3p; and an analysis step of analyzing the state of a specific disease and / or a specific physical constitution based on the quantified amount of microRNA.

[0024] (8) The disease / physique analysis method according to (7), wherein the sample is saliva or urine.

[0025] (9) A disease / physique analysis system comprising a measuring device and an analyzing device, wherein the measuring device is equipped with: a microRNA for miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205, miR-214, let-7a, miR-1229, miR-1246, miR-150, miR-223, miR-23a, miR-4644, miR-3976, miR-43 06, a measuring unit for quantifying at least one of miR-17-5p, miR-19a, miR-146a, miR-718, miR-375, miR-1290, miR-101, miR-373, miR-320, and miR-574-3p; and a sending unit for sending the amount of microRNA quantified by the above-mentioned measuring unit to an analyzing device, wherein the analyzing device comprises: a receiving unit for receiving the amount of the above-mentioned microRNA sent from the above-mentioned measuring device; and an analyzing unit for analyzing the state of a specific disease and / or a specific physical constitution based on the above-mentioned microRNA amount.

[0026] (10) A program for causing a computer to function as a unit for obtaining a protein expression of miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205, miR-214, let-7a, miR-1229, miR-1246, miR-150, miR-223, miR-23a, A unit for obtaining data on the amount of microRNA by quantifying at least one of miR-4644, miR-3976, miR-4306, miR-17-5p, miR-19a, miR-146a, miR-718, miR-375, miR-1290, miR-101, miR-373, miR-320, and miR-574-3p; and a unit for analyzing the state of a specific disease and / or a specific physical constitution based on the data on the amount of the above-mentioned microRNA.

[0027] (11) A computer-readable recording medium having a program for causing a computer to function as a unit for obtaining a protein expression of miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205, miR-214, let-7a, miR-1229, miR-1246, miR-150, miR-223, and miR-154 from among microRNAs present in exosomes extracted from a sample collected by a non-invasive method. -23a, miR-4644, miR-3976, miR-4306, miR-17-5p, miR-19a, miR-146a, miR-718, miR-375, miR-1290, miR-101, miR-373, miR-320, and miR-574-3p; and a unit for analyzing the state of a specific disease and / or a specific physical constitution based on the above-mentioned microRNA amount data.

[0028] (12) A disease / physique analysis method comprising: an extraction step of extracting exosomes from a saliva sample; a step of quantifying miR-103, miR-21 and / or miR-19 among the microRNAs present in the exosomes; and an analysis step of analyzing the state of a specific disease and / or a specific physical condition based on the amount of the microRNAs miR-103, miR-21 and / or miR-19.

[0029] (13) A disease / physique analysis system comprising a measuring device and an analyzing device, wherein the measuring device comprises: a measuring unit for quantifying the amount of miR-103, miR-21 and / or miR-19 in the microRNA present in exosomes extracted from a saliva sample; and a sending unit for sending the amount of miR-103, miR-21 and / or miR-19 microRNA quantified by the measuring unit to the analyzing device, wherein the analyzing device comprises: a receiving unit for receiving the amount of the microRNA sent from the measuring device; and an analyzing unit for analyzing the state of a specific disease and / or a specific physical condition based on the amount of the microRNA.

[0030] (14) A program for causing a computer to function as a unit that obtains data on the amounts of miR-103, miR-21, and / or miR-19 among the microRNAs present in exosomes extracted from a saliva sample; and a unit that analyzes the state of a specific disease and / or a specific physical constitution based on the data on the amounts of miR-103, miR-21, and / or miR-19.

[0031] (15) A computer-readable recording medium having a program for causing a computer to function as: a unit for obtaining data on the amount of microRNAs obtained by quantifying miR-103, miR-21, and / or miR-19 among microRNAs present in exosomes extracted from a saliva sample; and a unit for analyzing the state of a specific disease and / or a specific physical constitution based on the data on the amount of the above-mentioned microRNAs, miR-103, miR-21, and / or miR-19.

[0032] Effects of the Invention

[0033] According to the present invention, a disease / constitution analysis method, a disease / constitution analysis system, a program, and a computer-readable recording medium can be provided, which can analyze the risk of developing lifestyle diseases and the like using a sample collected by a simple method. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 This is a block diagram showing the system configuration of the disease / physique analysis system according to the first embodiment of the present invention.

[0035] Figure 2 This is a flowchart showing a disease / physique analysis method using the disease / physique analysis system according to the first embodiment of the present invention.

[0036] Figure 3 This is a diagram showing an example of the analysis results of diseases / physiques according to the first embodiment of the present invention.

[0037] Figure 4 This is a flowchart showing a disease / physique analysis method using the disease / physique analysis system according to the second embodiment of the present invention. DETAILED DESCRIPTION

[0038] Hereinafter, a disease / physique analysis method according to a first embodiment of the present invention will be described with reference to the drawings.

[0039] The disease / constitution analysis method of the first embodiment of the present invention includes: an extraction step of extracting RNA from a sample collected by non-invasive means; a step of quantifying mRNA related to the onset of a specific disease and / or a specific constitution among the mRNA present in the above-mentioned RNA; and an analysis step of analyzing the state of the above-mentioned specific disease and / or the above-mentioned specific constitution based on the quantified mRNA amount.

[0040] In addition, the disease / constitution analysis system of the first embodiment of the present invention includes a measuring device and an analyzing device, wherein the measuring device has a measuring unit that quantifies the amount of mRNA related to the onset of a specific disease and / or a specific constitution in RNA extracted from a sample collected using non-invasive means, and a sending unit that sends the amount of mRNA quantified by the above-mentioned measuring unit to the analyzing device, and the analyzing device has a receiving unit that receives the above-mentioned mRNA amount sent from the above-mentioned measuring device and an analyzing unit that analyzes the state of the above-mentioned specific disease and / or the above-mentioned specific constitution based on the above-mentioned mRNA amount.

[0041] Figure 1 1 is a block diagram showing the system configuration of the disease / physique analysis system according to the first embodiment of the present invention. Figure 1 As shown, the disease / physique analysis system 2 includes a quantitative PCR device 4 as a measuring device and a PC (personal computer) 6 as an analyzing device.

[0042] In addition, the quantitative PCR device 4 includes a control unit 8 that comprehensively controls each unit of the quantitative PCR device 4, and the control unit 8 is connected to an input unit 10 that accepts input operations such as measurement conditions and measurement start, a measurement unit 12 that amplifies and quantifies mRNA using specified primers, and a sending unit 14 that sends data on the mRNA amount measured by the measurement unit 12 to PC 6.

[0043] In addition, PC 6 has a CPU 16, to which is connected a receiving unit 18 for receiving data on the amount of mRNA sent from the quantitative PCR device 4, a storage unit 20 for storing the data on the amount of mRNA, an analyzing unit 22 for analyzing the state of the disease based on the data on the amount of mRNA, and an operating unit 24 for specifying data used in the analysis of the state of the disease and inputting instructions for starting the analysis of the disease, etc.

[0044] Next, refer to Figure 2 The flowchart shown explains a method for analyzing a disease / physique using the disease analysis system according to the embodiment of the present invention.

[0045] First, in the present invention, RNA is extracted from a sample collected by a non-invasive method to a living body (step S1). As a method for extracting RNA, a known method such as a centrifugal separation method, a suction filtration method, a method using an extraction reagent, an extraction kit, etc. can be used, but it is preferred to perform a treatment for stably storing RNA, or use a dry filter paper treated in a manner that can extract and stably store RNA, and it is more preferred to use a dry filter paper treated in a manner that can extract and stably store RNA.

[0046] Examples of treatments for stably storing RNA include treatments using RNAlater (registered trademark) or the like on collected samples.

[0047] Examples of such dry filter paper include RNASound RNA Sampling / Extracting Card (manufactured by Metammune).

[0048] In addition, examples of samples collected by non-invasive means include saliva, oral mucosa, urine, etc., preferably saliva and oral mucosa, and more preferably saliva.

[0049] Therefore, the sample can be easily transported by injecting it onto dry filter paper treated so that RNA can be extracted and stably stored, such as RNASound RNA sampling / extraction card, so that it adheres or adsorbs, and then the sample can be easily transported by injecting it onto dry filter paper treated so that RNA can be extracted and stably stored, and the like, and ... into dry filter paper, such as RNASound RNA sampling / extraction card, and the like.

[0050] When centrifugation, filtration or a method using an extraction reagent is used as the RNA extraction method, the container in which the sample is collected needs to be transported to an inspection agency or inspection room in a liquid state or the like. However, if a dry filter paper such as an RNASound RNA sampling / extraction card that has been treated so as to extract and stably preserve RNA is used, the RNASound RNA sampling / extraction card or other card or paper can be used as a medium to transport the sample to an inspection agency or inspection room. This is preferred from the perspective of ease of transportation such as ability to transport at room temperature and from the perspective of transportation cost.

[0051] When transporting the sample-attached filter paper, the sample may be placed in a predetermined bag or the like for transport from the viewpoint of odor prevention or the like.

[0052] Next, the amount of mRNA associated with the onset of a specific disease in the extracted RNA is quantified using a quantitative PCR device 4 (step S2). When quantification is performed, first, the RNA extracted in step S1 is set in the measuring unit 12. Then, when the operator inputs an instruction to start quantification from the input unit 10, the control unit 8 starts the quantification of mRNA for the RNA set in the measuring unit 12. Here, in the quantitative PCR device 4, it is preferred to measure the real-time PCR based on the amplification of the polymerase chain reaction (PCR) over time. In addition, primers designed for mRNA associated with the onset of a specific disease and / or a specific constitution can be used for amplification. In addition, as a control for the analysis of the expression level of mRNA, housekeeping genes such as GAPDH are used.

[0053] In this embodiment, specific diseases include cancer, arteriosclerosis, cerebral infarction, myocardial infarction, immune function-related diseases, autoimmune diseases, type I diabetes, type II diabetes, hyperlipidemia, thrombosis, bulimia, sweets intake, obesity, metabolic syndrome, cholesterol-related diseases, neutral fat-related diseases, liver cirrhosis, kidney stones, cholelithiasis, urolithiasis, emphysema, nicotine dependence, bone disease, inflammation, rheumatoid arthritis, gout, back pain, duodenal ulcer, anemia, rhinitis, restless legs syndrome, cluster headache, migraine, age-related macular degeneration, glaucoma, astigmatism, skin aging, atopy, sun spots, freckles, fatigue, chronic fatigue, alopecia areata, etc. In addition, specific constitutions such as detoxification, drug resistance, alcohol metabolism, caffeine metabolism, exercise therapy, sleep time, and longevity can also be analyzed.

[0054] Examples of mRNAs associated with the onset of cancer include p53, a gene that suppresses various cancers; BRAF, a pro-oncogene; K-RAS, a sarcoma virus oncogene; cytokeratin-7, which is associated with lung cancer, gastric cancer, ovarian cancer, etc.; cytokeratin-19, which is associated with lung cancer, breast cancer, thyroid cancer, etc.; cytokeratin-20, which is associated with gastric cancer, colorectal cancer, pancreatic cancer, etc.; MAGE-A1, which is a tumor-specific antigen found in melanoma cells and is associated with lung cancer, gastric cancer, liver cancer, etc.; and cytokeratin-20, which is a tumor-specific antigen found in melanoma cells and is associated with lung cancer, gastric cancer, liver cancer, etc. MAGE-A3 is a tumor-specific antigen found in melanoma cells and is associated with lung cancer, gastric cancer, breast cancer, etc.; MAGE-A12 is a tumor-specific antigen found in melanoma cells and is associated with esophageal cancer and breast cancer; HnRNP is a nuclear lipoprotein that is mainly associated with lung cancer and has also been confirmed to be associated with breast cancer, etc.; Mucin-1 is a mucus glycoprotein that is associated with esophageal cancer, colorectal cancer, pancreatic cancer, etc.; CEA is used as a tumor marker and is expressed in embryonic cell adhesion, colorectal cancer, lung cancer, pancreatic cancer, etc. The mRNA of each, etc.

[0055] In addition, examples of mRNAs associated with arteriosclerosis include endothelin, which is produced in an increased manner when cardiovascular diseases such as hypertension and arteriosclerosis occur; VCAM-1, an adhesion molecule found in arteriosclerotic foci, which is believed to be necessary for the onset of arteriosclerosis due to inflammation of the cell wall and the accompanying adhesion of leukocytes to vascular endothelial cells; ICAM-1, a molecule that is a receptor associated with the adhesion mechanism of monocytes and lymphocytes to vascular endothelial cells and causes strong adhesion; P-selectin, which is associated with the reaction system when oxidized LDL produced by oxidation of LDL on vascular endothelial cells is infinitely taken up by macrophages, causing macrophages to become foam cells and thus forming plaques; M-CSF, which is closely associated with the early stages of arteriosclerosis; LOX-1, which is suggested to play an important role in the mechanism of organ dysfunction caused by various risk factors for arteriosclerosis; and mRNAs of thrombin R, which is associated with the onset and progression of various vascular diseases such as arteriosclerosis, restenosis after angioplasty, cerebral vasospasm after subarachnoid hemorrhage, vasculitis, thromboangiitis obliterans, and pulmonary hypertension.

[0056] In addition, examples of mRNAs related to the onset of cerebral infarction include mRNAs of the gene NINJ2, which is related to the onset of cerebral infarction and the cerebrovascular system.

[0057] In addition, examples of mRNAs associated with the onset of myocardial infarction include CDKN2B-AS1 mRNA present in the CDKN2B-CDKN2A gene cluster on chromosome 9, which plays a role in cell proliferation and is reported to be strongly associated with familial cardiovascular disorders.

[0058] In addition, examples of mRNAs associated with the onset of diseases related to immune function include mRNAs of TNF-α, which can determine whether or not a person has a genetic tendency to have high immunity.

[0059] In addition, examples of mRNAs associated with the onset of autoimmune diseases include mRNAs of IL-6, NF-κB, FKBP5, KLF5, and Foxp3, which belong to a gene group associated with a reaction in which a self-forming substance is immune-identified as a foreign substance and causes a rejection reaction.

[0060] In addition, examples of mRNAs related to the onset of diabetes (type I and type II) include mRNAs of PPAR-γ, glucokinase, HNF-4α, adiponectin, and TNF-α, which belong to gene groups related to sugar metabolism and fat metabolism.

[0061] In addition, examples of mRNAs related to the onset of type II diabetes mainly include mRNAs of SORBS1, LMNA, and UCP2, which belong to a gene group related to pancreatic functions such as insulin secretion and glucose metabolism.

[0062] In addition, examples of mRNAs associated with the onset of hyperlipidemia include PCSK9, which is reported to be the third causative gene for familial hypercholesterolemia, cholesteryl ester transfer protein CETP, and LCAT mRNAs associated with primary hyperlipoproteinemia, obesity, diabetes, and nephrotic syndrome.

[0063] In addition, examples of mRNAs related to the onset of thrombosis include mRNAs of genes ABO related to blood coagulation.

[0064] In addition, examples of mRNAs related to the onset of bulimia include mRNAs of RUFY1, which is involved in the transport of lipids and proteins in cells.

[0065] In addition, examples of mRNAs related to the onset of sweets intake include mRNAs of ADRA2A, which is a gene that receives adrenaline and increases blood sugar levels, and can determine whether or not there is a tendency to consume a lot of sweets.

[0066] In addition, examples of mRNAs associated with the onset of obesity include mRNAs of a thrifty gene β3AR called β3-adrenaline receptor gene, a thermogenic protein UCP1 that burns fat, and a thrifty gene β2AR called β2-adrenaline receptor gene.

[0067] In addition, examples of mRNAs associated with the onset of metabolic syndrome include mRNAs of the gene APOE that is associated with the level of risk of dyslipidemia, and mRNAs of the gene ACE that is associated with the level of risk of hypertension.

[0068] In addition, examples of mRNAs associated with the onset of cholesterol-related diseases such as hypercholesterolemia include mRNAs of the gene ABCG8 associated with the metabolism of bad cholesterol (LDL).

[0069] In addition, examples of mRNAs related to the onset of neutral fat-related diseases include mRNAs of APOA5, a gene related to the decomposition of neutral fat, and GCKR, a gene related to sugar or lipid metabolism.

[0070] In addition, examples of mRNA associated with the onset of liver cirrhosis include mRNA of the gene TNPO3, which is involved in primary biliary cirrhosis, in which the bile duct is destroyed and bile refluxes into the liver.

[0071] In addition, examples of mRNAs associated with the onset of kidney stones include DGKH mRNA and the like.

[0072] In addition, examples of mRNAs related to the onset of cholelithiasis include mRNAs of the gene ADRB3, which plays a key role in initiating lipolysis and is associated with the susceptibility of visceral fat accumulation.

[0073] In addition, examples of mRNA associated with the onset of urolithiasis include mRNA of the gene UMOD associated with calcium deposition in the urinary tract system.

[0074] In addition, examples of mRNAs associated with the onset of emphysema include mRNAs of CSMD1 and emphysema-susceptibility gene BICD1.

[0075] In addition, examples of mRNAs related to the onset of nicotine dependence include mRNAs of genes such as CHRNA3 that are related to nicotine responsiveness and metabolism.

[0076] In addition, examples of mRNAs related to the onset of bone diseases include mRNAs of VDR, a nuclear receptor for vitamin D and a gene related to bone metabolism, and BGLAP, a non-collagenous protein of bone and a gene related to bone formation by osteocalcin.

[0077] In addition, examples of mRNAs related to the onset of inflammation include mEPHX1 mRNA, which can determine whether an inflammatory substance is likely to cause inflammation in vivo.

[0078] In addition, examples of mRNAs associated with the onset of rheumatoid arthritis include mRNAs of the gene group PADI4, which causes severe pain and swelling in joints throughout the body, including the hands and feet.

[0079] In addition, examples of mRNAs associated with the onset of arthritis include mRNA of DVWA and the like.

[0080] In addition, examples of mRNA associated with the onset of gout include mRNA of the gene SLC2A9 associated with the excretion of uric acid.

[0081] In addition, examples of mRNAs associated with the onset of low back pain include mRNAs of the gene CILP associated with cartilage repair.

[0082] In addition, examples of mRNAs associated with the onset of duodenal ulcers include mRNAs of genes such as PSCA that are associated with the mucosa of the stomach and small intestine.

[0083] In addition, examples of mRNAs associated with the onset of anemia include mRNAs of IGL, a gene associated with iron transport in blood.

[0084] In addition, examples of mRNAs associated with the onset of rhinitis include mRNAs of GSDMB, which have been reported to be associated with nasal congestion and the risk of developing asthma.

[0085] In addition, examples of mRNA associated with the onset of restless legs syndrome include mRNA of the gene BTBD9 associated with symptoms such as itching and pain in the feet.

[0086] In addition, examples of mRNAs associated with the onset of cluster headache include HCRtr2 mRNA and the like.

[0087] In addition, examples of mRNAs associated with the onset of migraine include mRNA of PRDM16 and the like.

[0088] In addition, examples of mRNAs associated with the onset of age-related macular degeneration include CFH and the like.

[0089] In addition, examples of mRNAs related to the onset of glaucoma include mRNAs of CDKN2B, which is one of the gene groups related to intraocular pressure and lens function.

[0090] In addition, examples of mRNA associated with the onset of astigmatism include mRNA of PDGFRA, which is found to be highly expressed in humans with corneal astigmatism.

[0091] In addition, examples of mRNAs related to the onset of skin aging include mRNAs of the enzyme MMP1 that decomposes collagen, mRNAs of the gene GPX1 that is a toxic substance filtering gene and is related to the detoxification of toxic substances that affect skin aging, and mRNAs of the gene SOD2 that is a stress metabolism gene and is related to the removal of active oxygen that affects skin aging.

[0092] In addition, examples of mRNAs associated with the onset of atopy include mRNAs of FLG, SPINK5, and ZNF365, each of which belongs to the gene group of the immune system.

[0093] In addition, examples of mRNAs associated with the onset of sun spots include mRNAs of the gene ASIP associated with melanin production.

[0094] In addition, examples of mRNAs related to the onset of freckles include mRNAs of the gene IRF4 that can determine the susceptibility to the occurrence of freckles.

[0095] In addition, examples of mRNAs related to the onset of fatigue include mRNAs of the gene NQO1 related to the production of ubiquinone (coenzyme Q10) for burning energy in the body.

[0096] In addition, examples of mRNAs associated with the onset of chronic fatigue include mRNAs of TPH2, a gene associated with the production of the neurotransmitter serotonin.

[0097] In addition, examples of mRNA associated with the onset of alopecia areata include mRNA of CTLA4, which is considered to be one of the causative genes associated with hair loss caused by autoimmune diseases.

[0098] In addition, examples of mRNAs related to detoxification include mRNAs of the gene GPX1 related to the treatment of active oxygen species.

[0099] In addition, examples of mRNA associated with drug resistance include mRNA of multidrug resistance protein and the like.

[0100] In addition, examples of mRNAs related to alcohol metabolism include mRNAs of PEPCK, and aldehyde dehydrogenase and acetaldehyde dehydrogenase, which are genes of enzymes related to alcohol metabolism.

[0101] In addition, examples of mRNAs related to caffeine metabolism include mRNAs of CYP1A2, which can determine the magnitude of the effects of caffeinated beverages on physical fitness.

[0102] In addition, examples of mRNAs related to exercise therapy include mRNAs of genes such as AMP kinase, GLUT4, and PGC-1α, which are related to insulin resistance, sugar metabolism, and fat burning in mitochondria.

[0103] In addition, examples of mRNA associated with sleep time include mRNA of NRSR1, which can determine whether or not one has a genetic tendency to have a biological clock, particularly a delayed bedtime.

[0104] In addition, examples of mRNAs associated with longevity include mRNAs of FOXO3 and the like which are associated with energy consumption of mitochondria (Mitochondria) and mitochondria in cells, and a rise in body temperature.

[0105] That is, examples of mRNA to be quantified in the present invention include the above-mentioned mRNAs.

[0106] Next, the control unit 8 of the quantitative PCR device 4 transmits the data of the mRNA amount obtained by the quantification to the PC 6 via the transmission unit 14 (step S3), and the PC 6 receives the data of the mRNA amount obtained by the quantification via the reception unit 18 (step S4). Here, the communication between the transmission unit 14 of the quantitative PCR device 4 and the reception unit 18 of the PC 6 can be performed by wired communication such as a wired LAN, or by wireless communication such as a wireless LAN or Bluetooth (registered trademark).

[0107] Next, the CPU 16 of the PC 6 stores the mRNA amount data received by the receiving unit 18 in the storage unit 20 (step S5). Here, the mRNA amount data is stored in the storage unit 20 in association with, for example, the sample ID, measurement date, and measurement number.

[0108] Then, when the data of the analysis object is designated by the operation unit 24 and an instruction to start the analysis is input, the CPU 16 causes the analysis unit 22 to analyze the state of the specific disease / physique (step S6). It should be noted that when analyzing the state of the specific disease / physique, the CPU 16 reads the data designated as the analysis object from the data of the amount of mRNA stored in the storage unit 20, and causes the analysis unit 22 to analyze the state of the specific disease / physique. An example of the analysis result is shown in Figure 3 .

[0109] Here, the amount of mRNA quantified using the quantitative PCR device 4 can be analyzed by statistical processing, preferably by statistically processing the obtained data using the comparative Ct method. For example, by continuously quantifying mRNA extracted from a sample of a specific person and collecting data at normal times, when the amount of mRNA changes relative to the data, it can be analyzed that there is a risk of developing a specific disease, and it can also be analyzed that there is a tendency to develop a specific constitution.

[0110] In addition, as the mRNA amount, the cycle number at which the mRNA was detectable by quantitative PCR was used, and the value corrected by the expression level of GAPDH was used.

[0111] In the analysis of the state of a specific disease / physique performed using the analysis unit 22, for example, data continuously collected from a specific individual is used. Thus, when the amount of mRNA related to the onset of a specific disease / specific constitution changes compared to the continuously collected data, it can be analyzed as having a risk of developing the specific disease, and further, it can be analyzed as having a tendency to develop a specific constitution.

[0112] In addition, when analyzing the state of a specific disease / physique, a predetermined threshold value may be used for analysis. In this case, the amount of mRNA related to the onset of a specific disease / specific physique is statistically processed from all data or randomly extracted data in the amount of mRNA stored in the storage unit 20, thereby precalculating a threshold value for analyzing the onset of a specific disease / specific physique. Then, the threshold value is set as the threshold value when analyzing the state of a specific disease / specific physique, thereby enabling analysis of whether the specific data is the state of a specific disease / specific physique.

[0113] It should be noted that in the above-mentioned analysis of the state of a specific disease / specific constitution, the analysis of the state of a specific disease / specific constitution may be performed after removing data such as outliers and missing values.

[0114] According to the disease / physique analysis method and disease / physique analysis system of the first embodiment of the present invention, it is possible to analyze the risk of developing a disease such as a lifestyle disease using a sample collected by a simple method.

[0115] It should be noted that, in the first embodiment, PC 6 is used as an example of an analysis device, but a tablet terminal or the like may also be used as an analysis device. In addition, the disease / physique analysis system 2 is described as an example of a configuration including two devices, a quantitative PCR device 4 and a PC 6, but the analysis system may also be configured using one device, for example, by incorporating the function of the analysis device into the quantitative PCR device 4.

[0116] In addition, in the first embodiment, the configuration is such that data on the amount of mRNA is sent from the quantitative PCR device 4 as a measuring device to the PC 6 as an analyzing device. However, in a case where communication between the quantitative PCR device 4 and the PC 6 is impossible, the data on the amount of mRNA can be transferred from the quantitative PCR device 4 to the PC 6 via a recording medium such as a USB memory or an SD card.

[0117] In addition, in the first embodiment described above, the configuration in which the PC 6 analyzes the state of a specific disease / specific constitution when the data of the analysis object is designated by the operation unit 24 and the instruction to start the analysis is inputted is described, but an analysis program for analyzing the state of a specific disease / specific constitution based on the data of the amount of mRNA related to the specific disease / specific constitution in the mRNA extracted from the sample can be downloaded through a network such as the Internet and incorporated into a computer, thereby enabling the computer to perform the above-mentioned analysis processing. Here, the analysis program can read the data of the amount of mRNA related to the onset of a specific disease and / or a specific constitution stored on the network or on the computer, and use it for the analysis of the state of the specific disease / specific constitution.

[0118] In addition, the program can also be recorded in a computer-readable recording medium such as a floppy disk, CD-ROM, DVD, etc. That is, it can be read from a computer-readable recording medium and programmed into a computer, thereby enabling the computer to perform the function of analyzing the state of the above-mentioned specific disease / physique.

[0119] Next, the disease / physique analysis method of the second embodiment of the present invention is described with reference to the accompanying drawings. It should be noted that the disease / physique analysis method of the second embodiment is changed to the following structure: microRNA is used instead of mRNA used in the first embodiment. Therefore, for the same structure as the first embodiment, the detailed description is omitted, and only the different parts are described in detail.

[0120] The disease / physique analysis method of the second embodiment of the present invention comprises: extracting exosomes from a sample collected by non-invasive means; analyzing the microRNAs present in the exosomes, including miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205, miR-214, let-7a, miR-1229, miR-1246, miR-150, miR-223, and miR- 23a, miR-4644, miR-3976, miR-4306, miR-17-5p, miR-19a, miR-146a, miR-718, miR-375, miR-1290, miR-101, miR-373, miR-320, and miR-574-3p; and an analysis step of analyzing the onset of a specific disease and / or the state of a specific physical constitution based on the quantified amount of microRNA.

[0121] In addition, the disease / physique analysis system of the second embodiment of the present invention includes a measuring device and an analyzing device, wherein the measuring device has a method for detecting miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205, miR-214, let-7a, miR-1229, miR-1246, miR-150, miR-223, miR-23a, miR-4644, miR-3976 ... R-4306, miR-17-5p, miR-19a, miR-146a, miR-718, miR-375, miR-1290, miR-101, miR-373, miR-320, miR-574-3p measuring unit and the amount of microRNA quantitatively sent to the analysis device sending the analysis device has a receiving unit for receiving the amount of microRNA sent from the measuring device and an analysis unit for analyzing the state of a specific disease and / or a specific physical constitution based on the amount of microRNA.

[0122] In addition, the disease / constitution analysis method of the second embodiment of the present invention includes: an extraction step of extracting exosomes from a saliva sample; a step of quantifying miR-103, miR-21 and / or miR-19 among the microRNAs present in the above-mentioned exosomes; and an analysis step of analyzing the state of a specific disease and / or a specific constitution based on the amount of microRNA of miR-103, miR-21 and / or miR-19.

[0123] In addition, the disease / constitution analysis system of the second embodiment of the present invention includes a measuring device and an analyzing device, wherein the measuring device has a measuring unit that quantifies the amount of miR-103, miR-21 and / or miR-19 microRNA in the microRNA present in the exosomes extracted from the saliva sample, and a sending unit that sends the amount of miR-103, miR-21 and / or miR-19 microRNA quantified by the above-mentioned measuring unit to the analyzing device, and the analyzing device has a receiving unit that receives the above-mentioned microRNA amount sent from the above-mentioned measuring device, and an analyzing unit that analyzes the state of a specific disease and / or a specific constitution based on the above-mentioned microRNA amount.

[0124] The disease / physique analysis system of the second embodiment uses the system used in the first embodiment. Figure 1 The analysis system shown.

[0125] Next, refer to Figure 4 The flowchart shown explains a method for analyzing a disease / physique using the disease analysis system according to the embodiment of the present invention.

[0126] First, in the present invention, a sample collected by a non-invasive method to a living body is used to extract exosomes from the sample (step S11). As a method for extracting exosomes, ultracentrifugation, ultrafiltration, gel filtration, HPLC, or a method using an extraction reagent can be cited, but it is preferred to use a filter paper treated in a manner that can capture exosomes.

[0127] Examples of such filter paper include FTA microcards (manufactured by GE Healthcare) (see, for example, U.S. Patents 5,496,562, 5,756,126, 5,807,527, 5,972,386, and 5,985,327). The FTA microcards have filter paper on which a composition containing a weak base such as trimethylolmethane, a chelating agent such as ethylenediaminetetraacetate, an anionic surfactant such as sodium lauryl sulfate, and a free radical scavenger such as uric acid or urate is adsorbed or absorbed onto cellulose-based paper.

[0128] It should be noted that the filter paper constituting the FTA microcard is designed to entangle and capture nucleic acids, but according to the research of the present inventors, it is known that exosomes can be captured when a sample is injected or attached to the FTA microcard.

[0129] Therefore, the urine sample can be easily transported in this state (hereinafter sometimes referred to as "sample-attached filter paper") by injecting it onto a filter paper treated so as to capture exosomes, such as an FTA microcard, so that the sample adheres or is adsorbed.

[0130] When ultracentrifugation, ultrafiltration, gel filtration, HPLC or a method using an extraction reagent is used as a method for extracting exosomes, the container in which the sample is collected needs to be transported to an inspection agency or inspection room in a liquid state, etc. However, if filter paper treated in a manner capable of capturing exosomes is used, it can be transported to an inspection agency or inspection room using a card or paper such as an FTA microcard as a medium, which is preferred from the perspective of ease of transportation such as being able to be transported at room temperature and from the perspective of transportation cost.

[0131] When transporting the sample-attached filter paper, the sample may be placed in a predetermined bag or the like for transport from the viewpoint of odor prevention or the like.

[0132] In addition, examples of samples collected by non-invasive means include saliva and urine, and saliva is more preferable.

[0133] Next, after the exosomes are extracted from the sample in the extraction step, the microRNA is taken out from the exosomes (step S12). There is no particular limitation on the method for taking out microRNA from exosomes, and various commercially available extraction kits can be used. For example, the miRCURY RNA Isolation Kit (Product No. 300110; EXIQON) can be used.

[0134] Next, the amount of the extracted microRNA is quantified using the quantitative PCR device 4 (step S13). When quantification is performed, first, the microRNA taken out in step S12 is set in the measuring unit 12. Then, when the operator inputs an instruction to start quantification from the input unit 10, the control unit 8 starts the quantification of the microRNA set in the measuring unit 12. Here, in the quantitative PCR device 4, it is preferred to measure the real-time PCR based on the amplification of the polymerase chain reaction (PCR) over time. In addition, primers designed for microRNAs related to the onset of a specific disease and / or a specific constitution can be used for amplification. In addition, as a control for the expression analysis of the microRNA, a specified microRNA can be used.

[0135] In the second embodiment, examples of the specific disease / specific constitution include cancers such as ovarian cancer, colon cancer, pancreatic cancer, cervical cancer, liver cancer, prostate cancer, oropharyngeal squamous cell carcinoma, breast cancer, glioma, and glioblastoma multiforme.

[0136] Examples of microRNAs associated with the onset of ovarian cancer include miR-21, miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205, miR-214, and miR-373.

[0137] In addition, examples of microRNAs associated with the onset of colorectal cancer include let-7a, miR-1229, miR-1246, miR-150, miR-21, miR-223, miR-23a, and miR-19a.

[0138] In addition, examples of microRNAs associated with the onset of pancreatic cancer include miR-1246, miR-4644, miR-3976, miR-4306, and miR-21.

[0139] In addition, examples of microRNAs associated with the onset of cervical cancer include miR-21 and miR-146a.

[0140] In addition, examples of microRNAs associated with the onset of liver cancer include miR-21 and miR-718.

[0141] In addition, examples of microRNAs associated with the onset of prostate cancer include miR-375, miR-141, and miR-1290.

[0142] In addition, examples of microRNAs associated with the onset of oropharyngeal squamous cell carcinoma include miR-21 and the like.

[0143] In addition, examples of microRNAs associated with the onset of breast cancer include miR-101 and miR-373.

[0144] In addition, examples of microRNAs associated with the onset of glioma include miR-21 and the like.

[0145] In addition, examples of microRNAs associated with the onset of glioblastoma multiforme include miR-320 and miR-574-3p.

[0146] In the present embodiment, the microRNA to be quantified may be miR-103, miR-21, and / or miR-19 among the microRNAs present in the exosomes extracted from the saliva sample.

[0147] Here, miR-103 is a microRNA stably expressed in serum / plasma, urine, and exosomes in cerebrospinal fluid (for example, refer to Table 6 (page 25) of http: / / www.exiqon.com / ls / Documents / Scientific / microRNA-serum-plasma-guidelines.pdf).

[0148] In addition, miR-21 is a microRNA contained in exosomes extracted from serum or cerebrospinal fluid, and is found as a disease-specific molecule in a wide range of cancers, including ovarian cancer, colorectal cancer, pancreatic cancer, cervical cancer, liver cancer, oropharyngeal squamous cell carcinoma, and glioma. In other words, it is a type of microRNA that is secreted in large quantities by a wide range of cancer cells.

[0149] Here, there are microRNAs of the type that are stably expressed in exosomes in serum / plasma, saliva, and cerebrospinal fluid, such as the above-mentioned miR-103, and there are also microRNAs that are not stably expressed (same as above, for example, refer to Table 6 (page 25) of http: / / www.exiqon.com / ls / Documents / Scientific / microRNA-serum-plasma-guidelines.pdf). Therefore, even if it is expressed as a microRNA of the type contained in exosomes extracted from serum, cerebrospinal fluid, etc., it cannot be said that it is expressed as a microRNA of the type contained in exosomes extracted from saliva and urine. That is, no complete correlation has been confirmed between the types of microRNAs contained in exosomes extracted from serum, cerebrospinal fluid, etc. and the types of microRNAs contained in exosomes extracted from saliva.

[0150] In addition, miR-19 is a type of microRNA whose secretion is suppressed in a wide range of cancer cells, and the expression level of this type of microRNA contained in exosomes extracted from the serum or cerebrospinal fluid of cancer patients is reduced.

[0151] Next, the control unit 8 of the quantitative PCR device 4 transmits the data of the amount of microRNA obtained by the quantitative determination to the PC 6 via the transmission unit 14 (step S14), and the PC 6 receives the data of the amount of microRNA obtained by the quantitative determination via the reception unit 18 (step S15). Here, the communication between the transmission unit 14 of the quantitative PCR device 4 and the reception unit 18 of the PC 6 can be performed by wired communication such as a wired LAN, or by wireless communication such as a wireless LAN or Bluetooth (registered trademark).

[0152] Next, the CPU 16 of the PC 6 stores the microRNA amount data received by the receiving unit 18 in the storage unit 20 (step S16). Here, the microRNA amount data is stored in the storage unit 20 in association with, for example, the sample ID, measurement date, and measurement number.

[0153] Then, when the data of the analysis object is designated by the operation unit 24 and an instruction to start the analysis is input, the CPU 16 causes the analysis unit 22 to analyze the state of the specific disease and / or the specific constitution (step S17). It should be noted that when analyzing the state of the specific disease and / or the specific constitution, the CPU 16 reads the data designated as the analysis object from the data of the amount of microRNA stored in the storage unit 20, and causes the analysis unit 22 to analyze the state of the specific disease and / or the specific constitution.

[0154] Here, the amount of microRNA quantified using the quantitative PCR device 4 can be analyzed by statistical processing, preferably using the comparative Ct method to perform statistical processing on the obtained data for analysis. For example, by continuously quantifying the microRNA contained in the exosomes extracted from the sample of a specific person and collecting data at normal times (e.g., when non-cancer), when the amount of microRNA is confirmed to change relative to the data, it can be analyzed as having a risk of developing a specific disease, and in addition, it can be analyzed as having a tendency to become a specific constitution. It should be noted that when the amount of, for example, miR-21 and miR-19 is used as the amount of microRNA, the amount of miR-21 and the amount of miR-19 are analyzed using the values ​​compared with the amount of miR-103.

[0155] In the analysis of the state of a specific disease and / or a specific constitution performed using the analysis unit 22, for example, data continuously collected from a specific individual is used. Thus, when the amount of mRNA related to the onset of a specific disease / specific constitution changes compared to the continuously collected data, it can be analyzed as having a risk of developing the specific disease, and further, it can be analyzed as having a tendency to develop a specific constitution.

[0156] In addition, when analyzing the state of a specific disease and / or a specific constitution, a predetermined threshold value may also be used for analysis. In this case, the amount of microRNA related to the onset of a specific disease / specific constitution is statistically processed by all data or randomly extracted data in the amount of microRNA stored in the storage unit 20, thereby precalculating a threshold value for analyzing the onset of a specific disease / specific constitution. Then, the threshold value is set as the threshold value when analyzing the state of a specific disease / specific constitution, thereby enabling analysis of whether the specific data is the state of a specific disease / specific constitution.

[0157] It should be noted that in the analysis of the status of the specific disease / specific constitution described above, the status of cancer may be analyzed after removing data such as outliers and missing values.

[0158] According to the disease / physique analysis method and disease / physique analysis system of the second embodiment of the present invention, it is possible to analyze the risk of developing a disease such as a lifestyle disease using a sample collected by a simple method.

[0159] It should be noted that, in the above second embodiment, PC 6 is used as an example of an analysis device, but a tablet terminal or the like may also be used as an analysis device. In addition, as a disease / physique analysis system 2, a configuration including two devices, a quantitative PCR device 4 and a PC 6, is used as an example, but the analysis system may also be constituted by a single device, for example, by incorporating the function of the analysis device into the quantitative PCR device 4.

[0160] In addition, in the second embodiment, the structure is set to send data on the amount of microRNA from the quantitative PCR device 4 as a measuring device to the PC6 as an analyzing device. However, in the case where communication between the quantitative PCR device 4 and the PC6 is impossible, the data on the amount of microRNA can also be transferred from the quantitative PCR device 4 to the PC6 via a recording medium such as a USB memory or an SD card.

[0161] In addition, in the above embodiment, the configuration in which the PC 6 analyzes the state of a specific disease / specific constitution when the data of the analysis object is specified by the operation unit 24 and the instruction to start the analysis is input is described, but an analysis program for analyzing the state of a specific disease / specific constitution based on the data of the amount of mRNA related to a specific disease / specific constitution in the microRNA present in the exosomes extracted from the sample can be downloaded through a network such as the Internet and incorporated into a computer, thereby enabling the computer to perform the above-mentioned analysis processing. Here, the analysis program can read the data of the amount of microRNA related to the onset of a specific disease and / or a specific constitution stored on the network or on the computer, and use it for the analysis of the state of the specific disease / specific constitution.

[0162] In addition, the program can also be recorded in a computer-readable recording medium such as a floppy disk, CD-ROM, DVD, etc. That is, it can be read from a computer-readable recording medium and programmed into a computer, thereby enabling the computer to perform the function of analyzing the state of the above-mentioned specific disease / physique.

[0163] Description of symbols

[0164] 2 ... disease / physique analysis system, 4 ... quantitative PCR device, 6 ... PC, 8 ... control unit, 12 ... measurement unit, 16 ... CPU, 20 ... storage unit, 22 ... analysis unit

Claims

1. A method for analyzing physical constitution for non-disease diagnosis purposes, comprising: Extraction steps for extracting exosomes from samples collected using non-invasive means; A step of quantifying at least one of miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205, miR-214, let-7a, miR-1229, miR-1246, miR-150, miR-223, miR-23a, miR-4644, miR-3976, miR-4306, miR-17-5p, miR-19a, miR-146a, miR-718, miR-375, miR-1290, miR-101, miR-373, miR-320, and miR-574-3p among the microRNAs present in the exosomes; and An analysis step for analyzing the state of a specific constitution based on the quantified amount of microRNA.

2. The method for analyzing physical constitution for non-disease diagnosis purposes according to claim 1, wherein: The sample is saliva or urine.

3. A disease / physique analysis system, comprising a measuring device and an analyzing device, The measuring device comprises: a measuring unit for quantifying at least one of miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205, miR-214, let-7a, miR-1229, miR-1246, miR-150, miR-223, miR-23a, miR-4644, miR-3976, miR-4306, miR-17-5p, miR-19a, miR-146a, miR-718, miR-375, miR-1290, miR-101, miR-373, miR-320, and miR-574-3p among microRNAs present in exosomes extracted from a sample collected by a non-invasive method; and sending the amount of microRNA determined by the measuring unit to a sending unit of an analysis device, The analysis device comprises: a receiving unit that receives the amount of the microRNA transmitted from the measuring device; and An analysis unit analyzes the state of a specific disease and / or a specific constitution based on the amount of the microRNA.

4. A program for causing a computer to function as the following unit, wherein: a unit for acquiring data on the amount of microRNA obtained by quantifying at least one of miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205, miR-214, let-7a, miR-1229, miR-1246, miR-150, miR-223, miR-23a, miR-4644, miR-3976, miR-4306, miR-17-5p, miR-19a, miR-146a, miR-718, miR-375, miR-1290, miR-101, miR-373, miR-320, and miR-574-3p among the microRNAs present in exosomes extracted from a sample collected by a non-invasive method; and A unit for analyzing the state of a specific disease and / or a specific physical constitution based on the data of the amount of the microRNA.

5. A computer-readable recording medium having recorded thereon a program for causing a computer to function as the following means: a unit for acquiring data on the amount of microRNA obtained by quantifying at least one of miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205, miR-214, let-7a, miR-1229, miR-1246, miR-150, miR-223, miR-23a, miR-4644, miR-3976, miR-4306, miR-17-5p, miR-19a, miR-146a, miR-718, miR-375, miR-1290, miR-101, miR-373, miR-320, and miR-574-3p among the microRNAs present in exosomes extracted from a sample collected by a non-invasive method; and A unit for analyzing the state of a specific disease and / or a specific physical constitution based on the data of the amount of the microRNA.

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