PTGIS gene mutation related to pulmonary hypertension and application thereof

A pulmonary arterial hypertension and genetic technology, applied in the fields of application, genetic engineering, plant gene improvement, etc., can solve the problems of unknown etiology of IPAH patients

Active Publication Date: 2018-01-19
FUWAI HOSPITAL CHINESE ACAD OF MEDICAL SCI & PEKING UNION MEDICAL COLLEGE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the known pathogenic genes are far from explaining the genetic etiology of all PAH patients, and the etiology of 60%-80% of IPAH patients is completely unknown

Method used

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  • PTGIS gene mutation related to pulmonary hypertension and application thereof
  • PTGIS gene mutation related to pulmonary hypertension and application thereof
  • PTGIS gene mutation related to pulmonary hypertension and application thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0075] research population

[0076] Patient group: Patients with pulmonary arterial hypertension were selected from Shanghai Pulmonary Hospital Affiliated to Tongji University and Fuwai Hospital of Chinese Academy of Medical Sciences. All patients underwent right heart catheterization. The diagnostic criteria for PAH were: resting mean pulmonary arterial pressure (mPAP) ≥ 25 mm Hg and pulmonary capillary wedge pressure (PCWP) ≤ 15 mm Hg and pulmonary vascular resistance (PVR) > 3 units. After excluding all known secondary factors causing PAH, the patient was diagnosed with idiopathic PAH. The point mutation of BMPR2 gene was detected by Snager sequencing, and the large fragment rearrangement of BMPR2 was detected by multiple ligation probe amplification technology. All patients with BMPR2 gene mutation were excluded, and 230 IPAH patients without BMPR2 mutation were finally selected. The 230 patients were divided into two "discovery (discovery)" and "validation (validation)" ...

Embodiment 2

[0097] Sanger sequencing was used to detect three mutation sites of PTGIS gene.

[0098] 1 Reagent: (1) Human Blood Genomic DNA Purification Kit DP318-02 (Tiangen Biochemical Technology, Beijing, China); (2) 10% SDS: 10.0g SDS was dissolved in 90ml water, adjusted to pH 7.2, added water to volume to 100ml; (3) TE: 10mM Tris-HCl (pH8.0), 1mM EDTA-Na2 (pH 8.0); (4) 50X TAE electrophoresis buffer: 242.0g Tris-HCl, 27.5ml glacial acetic acid, 100ml 0.5mM EDTA-Na2, final volume 1L; (5) Inhibitory endonucleases were purchased from New England Biolabs, USA; (6) All primers were purchased from Beijing Aoke Biological Company.

[0099]2 Instruments and equipment: (1) PCR instrument: DNA engine, Bio-Rad, USA; (2) Refrigerated centrifuge: RC-5C, SORVALL, USA; (3) Balance: JA5003 Shanghai Balance Instrument Factory; (4) Gel electrophoresis Slot: Beijing Liuyi Instrument Factory.

[0100] 3 operation steps:

[0101] 3.1 Genomic DNA was extracted from 4ml of peripheral blood using the Bl...

Embodiment 3

[0115] Animal model experiment, PTGIS expression level study in PAH rat model.

[0116] Two PAH rat models (monocrotine (MCT) and hypoxia) were used to study the relationship between the expression of PTGIS and pulmonary vascular remodeling. Normal rats were used as controls to detect mean pulmonary arterial pressure, right ventricular hypertrophy index and PTGIS mRNA expression level, the results are as follows Figure 4 Shown (in the figure: A is the change of mean pulmonary arterial pressure (mPAP) in hypoxia and MCT model rats (n=4-10); B is the change of right ventricular hypertrophy index in hypoxia and MCT model rats (n=4-10); C is the expression level of PTGIS gene mRNA detected by RT-PCR in the lung tissue of hypoxic and MCT rats (n=3-4); in the figure, "***" means P<0.001, The difference is extremely significant; "**" means P<0.01, the difference is significant).

[0117] Figure 4 -A shows that compared with the control group, the mean pulmonary artery pressure i...

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Abstract

The invention discloses a PTGIS gene mutation related to pulmonary hypertension and application thereof, relating to the field of pulmonary hypertension diseases. According to the invention, through whole genome sequencing, the condition that PTGIS gene has three PTGIS rare variants, namely c.755G more than A, c.1339G more than A and g.23867G more than A positioned at an intron-exon splicing site,which are tightly related to pulmonary hypertension is discovered. For the discovery, one the one hand, the pathogenesis of a patient suffering from pulmonary hypertension is explained favorably, andone the other hand, a mutant type PTGIS gene with the mutation site and corresponding mutation type PTGIS protein are taken as biomarkers of pulmonary hypertension, which can be used for evaluating the risk of the patient suffering from the pulmonary hypertension, or can be used for early warning that the descendant of a PTGIS mutant gene carrier has the risk of suffering from pulmonary hypertension before pregnancy; also the mutation site can be taken as a target point, thus providing a novel concept and measure for treating pulmonary hypertension.

Description

technical field [0001] The present invention relates to the field of pulmonary arterial hypertension disease, in particular, relates to the PTGIS gene mutation related to pulmonary arterial hypertension and its application. Background technique [0002] Pulmonary arterial hypertension (PAH) is a type of cardiovascular disease characterized by a progressive increase in pulmonary artery pressure and a gradual increase in pulmonary vascular resistance, eventually leading to right heart failure and death. PAH can present at any age, has insidious symptoms, and is difficult to diagnose. The pathological mechanism of PAH is very unclear, the prognosis of patients is poor, the median survival time is only 2.8 years, and the 5-year survival rate is only 21%. PAH has become an important public health problem in our country, bringing a heavy burden to society and families. [0003] Genetic variation is an important factor affecting the occurrence of PAH. At present, seven PAH patho...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/47C12N15/12C12Q1/6883C40B40/06
Inventor 荆志成王晓建蒋鑫徐希奇李素琪叶珏孙凯吴艳李静惠韩志岩
Owner FUWAI HOSPITAL CHINESE ACAD OF MEDICAL SCI & PEKING UNION MEDICAL COLLEGE
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