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血管紧张素原基因单核苷酸多态性及单倍型与印度东部人群高血压风险的关联。

Association of angiotensinogen gene SNPs and haplotypes with risk of hypertension in eastern Indian population.

作者信息

Purkait Pulakes, Halder Kalpataru, Thakur Sunil, Ghosh Roy Abhishikta, Raychaudhuri Pradip, Bhattacharya Sandip, Sarkar B N, Naidu J M

机构信息

DNA Laboratory, Anthropological Survey of India, Western Regional Center, Udaipur, 313001 Rajasthan India.

DNA Laboratory, Anthropological Survey of India, 27 Jawaharlal Nehru Road, Kolkata, 700016 India.

出版信息

Clin Hypertens. 2017 Mar 29;23:12. doi: 10.1186/s40885-017-0069-x. eCollection 2017.

Abstract

BACKGROUND

Angiotensinogen (AGT) enzyme comprises a vital module of RAAS system that effectively controls the blood pressure and related cardiovascular functions. Ample association studies have reported the importance of AGT variants in cardiovascular and non-cardiovascular adversities. But lately, owing to the complexity of the many anomalies, the haplotype based examination of genetic variation that facilitates the identification of polymorphic sites which are located in the vicinity of the causative polymorphic site, gets greater appreciation.

METHODS

In the present study, we have done genotype and haplotype analysis of AGT gene in reference to hypertension to confirm the association of the two in an Indian population. To accomplish this, we performed candidate SNPs analysis and construct possible haplotypes across the promoter and gene region in 414 subjects (256 Hypertensive cases and 158 controls).

RESULTS

We found four SNPs (rs11568020: A-152G and rs5050: A-20C in promoter; rs4762 and rs699 in exon2) and 3 haplotypes (H4, H7 and H8) that showed a stronger positive association with hypertension. The haplotype H2 was showing protective association with hypertension.

CONCLUSION

The results of the present study confirmed and reestablished the role of AGT gene variants and their haplotypes in the causation of hypertension in Indian population and showed that haplotypes can provide stronger evidence of association.

摘要

背景

血管紧张素原(AGT)酶是肾素-血管紧张素-醛固酮系统(RAAS)的一个重要组成部分,可有效控制血压及相关心血管功能。大量关联研究报道了AGT基因变异在心血管及非心血管疾病中的重要性。但最近,由于众多异常情况的复杂性,基于单倍型的基因变异检测受到了更多关注,这种检测有助于识别位于致病多态性位点附近的多态性位点。

方法

在本研究中,我们针对高血压对AGT基因进行了基因型和单倍型分析,以证实二者在印度人群中的关联性。为此,我们对414名受试者(256例高血压患者和158例对照)进行了候选单核苷酸多态性(SNP)分析,并构建了启动子和基因区域的可能单倍型。

结果

我们发现四个SNP(启动子区域的rs11568020:A-152G和rs5050:A-20C;外显子2中的rs4762和rs699)以及三个单倍型(H4、H7和H8)与高血压呈较强的正相关。单倍型H2与高血压呈保护性关联。

结论

本研究结果证实并重新确立了AGT基因变异及其单倍型在印度人群高血压发病中的作用,并表明单倍型可提供更强的关联证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9e45/5371191/06445468b4d4/40885_2017_69_Fig1_HTML.jpg

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