mRNA marker composition for diagnosing or predicting the progression of diabetic nephropathy and use thereof

Abstract

The present invention relates to an mRNA marker composition for the diagnosis or prediction of progression of diabetic nephropathy and the use thereof. The mRNA marker composition for diagnosing or predicting the progression of diabetic nephropathy according to an embodiment of the present invention comprises at least one of HBA2, HBA1, SLC9A3R1, GNAI3, HBB, ATP5MD, B2M, VMP1, and CHPF2.

Description

Technology Field

[0001] The present invention relates to an mRNA marker composition for diagnosing or predicting the progression of diabetic nephropathy and its use, and more specifically, to an mRNA marker composition for the early diagnosis of diabetic nephropathy and its use. Background Technology

[0003] Since diagnostic methods to predict the likelihood of diabetic complications in specific areas among diabetic patients have not yet been developed, patients face the difficulty of having to undergo annual examinations for all areas susceptible to complications; therefore, there is a need for the development of technology capable of precisely diagnosing diabetic complications in their early stages. The problem to be solved

[0005] To resolve the aforementioned problems, the present invention provides an mRNA marker composition for diagnosing or predicting the progression of diabetic nephropathy capable of precise diagnosis of diabetic nephropathy, and uses thereof. means of solving the problem

[0007] An mRNA marker composition for diagnosing or predicting the progression of diabetic nephropathy according to one aspect of an embodiment of the present invention comprises at least one of HBA2, HBA1, SLC9A3R1, GNAI3, HBB, ATP5MD, B2M, VMP1, and CHPF2. Effects of the invention

[0009] According to the proposed embodiment, there is an advantage in precisely diagnosing diabetic nephropathy. Brief explanation of the drawing

[0011] FIG. 1 is a diagram showing that marker combinations according to an embodiment of the present invention are suitable for the early diagnosis of diabetic nephropathy. Specific details for implementing the invention

[0012] The advantages and features of the present invention and the methods for achieving them will become clear by referring to the embodiments described below in detail together with the accompanying drawings. However, the present invention is not limited to the embodiments disclosed below but may be implemented in various different forms. These embodiments are provided merely to ensure that the disclosure of the present invention is complete and to fully inform those skilled in the art of the scope of the invention, and the present invention is defined only by the scope of the claims.

[0013] Although terms such as "first," "second," etc., are used to describe various components, it goes without saying that these components are not limited by these terms. These terms are used merely to distinguish one component from another. Therefore, it goes without saying that the first component mentioned below may also be the second component within the technical scope of the present invention.

[0014] Throughout the specification, the same reference numerals refer to the same components.

[0015] The features of each of the various embodiments of the present invention may be combined or combined with one another, either partially or wholly, and as will be fully understood by those skilled in the art, various technical interlocking and operation are possible, and each embodiment may be implemented independently of one another or together in an interlocking relationship.

[0016] Meanwhile, potential effects that may be expected from the technical features of the present invention that are not specifically mentioned in the specification of the present invention are treated as described in the specification, and since the embodiments are provided to more completely explain the present invention to those with average knowledge in the art, the contents illustrated in the drawings may be exaggerated compared to the actual embodiment of the invention, and detailed descriptions of configurations that are judged to unnecessarily obscure the gist of the present invention are omitted or described briefly.

[0017] Embodiments of the present invention will be described in detail below.

[0019] Diabetes mellitus is defined as a condition where the blood glucose level is 126 mg / dL or higher on an empty stomach and 200 mg / dL or higher two hours after a meal, and can be diagnosed as diabetes mellitus if the glycated hemoglobin (HbA1C) is 6.5% or higher.

[0020] In particular, since the prediabetes phase, during which blood sugar levels rise even before a diagnosis is made, is identifiable, one can recognize future vulnerability to diabetes and prepare in advance.

[0021] However, while many people are susceptible to diabetes—to the extent that one in three people in North America is diagnosed with prediabetes—there are cases where people do not recognize the severity of diabetes and do not know that they have prediabetes.

[0022] In addition, as average life expectancy increases in Korea, people have been suffering for a long time from various incurable diseases, and it has been found that about 30% of people in their 60s, or about one-third, develop diabetes.

[0023] In addition, Korea entered an aging society in 2002, and the proportion of the population aged 65 or older is expected to rise to about 15% of the total population by 2020.

[0024] Furthermore, due to rapid population aging, the duration of living with diabetes is increasing, and the number of people suffering from diabetic complications is rising rapidly, leading to a growing burden of medical expenses.

[0025] In particular, diabetes is a disease that leads to death due to various diabetic complications rather than the inherent danger of the disease itself, and since the mortality rate from diabetic complications in Korea is very high compared to other OECD countries, rapid diagnosis and management of diabetic complications are necessary.

[0027] According to statistical data compiled by the National Health Insurance Service in 2015, complications caused by diabetes include eye-related complications and kidney complications, and in addition, cardiovascular complications such as angina and stroke are also serious.

[0028] Despite these serious complications of diabetes, diagnostic methods to predict the likelihood of developing complications in specific areas among diabetic patients have not yet been developed, posing a challenge as patients must undergo annual examinations for all areas susceptible to such complications.

[0029] Accordingly, the development of technology capable of precisely diagnosing diabetes complications in their early stages is urgently needed.

[0030] In addition, diabetes is the most major cause of end-state renal disease, and as of 2011, the proportion of patients with end-state renal disease (ESRD) in the United States attributable to diabetes was reported to be over 50% (2013 American Society of Nephrology report), and the 10-year survival rate for end-state renal disease is very low at around 50%.

[0031] In addition, the proportion caused by diabetes continues to increase every year, and Korea's ESRD prevalence rate ranks third in the world, requiring a national response.

[0033] According to a report by the Korean Society of Nephrology, 50.2% of chronic kidney disease (CKD) cases in Korea are reported to be diabetic nephropathy, and since diabetic nephropathy occurs in between 20% and 40% of all diabetic patients, it is of utmost importance to identify precise diagnostic markers for the prevention and treatment of diabetic nephropathy.

[0034] Diabetic complications are broadly divided into macrovascular diseases, which damage the cerebrovascular system and cardiovascular system, and peripheral vascular diseases, which affect the retina and kidneys.

[0035] In particular, among diabetic complications, damage to the retina is not directly related to mortality, but cardiac complications or diabetic nephropathy are directly related to mortality, making precise diagnosis essential.

[0036] Among these, while the increasing trend of macrovascular disease associated with diabetes has slowed due to advancements in medications and medicine, the incidence of end-stage renal failure caused by diabetic nephropathy has not slowed or is even showing an increasing trend as life expectancy increases.

[0037] Furthermore, since cardiac complications are caused by various factors in addition to the effects of diabetes, it is difficult to precisely diagnose only diabetes-related cardiac complications among heart disease patients.

[0038] Accordingly, to accurately analyze only diabetes-related cardiac complications among heart disease patients, multifactor analysis using a very large cohort must be performed.

[0039] On the other hand, since more than 50% of end-stage renal failure is caused by diabetes, the association with diabetes is very high, so precise diagnosis can be utilized most effectively among diabetes complications.

[0040] In addition, while genetic factors such as eGFR are known to be associated with diabetes, the prevalence is low, and there are no definitive genetic markers known to be involved in predicting the onset and progression of diabetic nephropathy.

[0041] In addition, while the prediction of the onset and progression of diabetic nephropathy has so far relied on clinical evaluations centered on albuminuria and estimated glomerular filtration rate (eGFR), there are limitations in the early diagnosis of advanced diabetic nephropathy (annual eGFR decline rate > 3.3%) and in predicting progression to ESRD, thus requiring the development of new precision diagnostic technologies for diabetic nephropathy.

[0043] Accordingly, 24 marker combinations capable of early diagnosis of diabetic nephropathy were developed, and Figure 1 is a diagram showing that the marker combinations according to an embodiment of the present invention are suitable for early diagnosis of diabetic nephropathy.

[0044] Example 1; mRNA: HBA2, HBA1, SLC9A3R1, GNAI3, HBB, ATP5MD, B2M, VMP1, CHPF2

[0045] Example 2; miRNA: miR-148a-3p, miR-421, miR-16-5p, miR-424-5p

[0046] Third Example; Protein: AMBP, SERPINF2, RBP4, APOC3, CFHR2, VTN

[0047] 4th Example; SNP : rs78645179, rs79606005, rs186468483, rs56810132, rs142551240

[0048] According to the first to fourth embodiments proposed, diabetic nephropathy can be diagnosed early and precisely.

[0050] Although preferred embodiments of the present invention have been described above, the present invention is not limited thereto and can be implemented with various modifications within the scope of the claims, the detailed description of the invention, and the attached drawings, and it is obvious that such modifications also fall within the scope of the present invention.

Claims

Claim 1 An mRNA marker composition for diagnosing or predicting the progression of diabetic nephropathy is characterized by comprising at least one of HBA2, HBA1, SLC9A3R1, GNAI3, HBB, ATP5MD, B2M, VMP1, and CHPF2.

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