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LRP8基因中的甘油三酯单倍型与印度南部人群的心肌梗死有关。

TG haplotype in the LRP8 is associated with myocardial infarction in south Indian population.

作者信息

Asif Muhammed, Bhat Shivarama, Nizamuddin Sheikh, Mustak Mohammed S

机构信息

Department of Anatomy, Yenepoya Medical College and Hospital, Mangalore 575018, Karnataka, India.

Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India.

出版信息

Gene. 2018 Feb 5;642:225-229. doi: 10.1016/j.gene.2017.10.037. Epub 2017 Oct 12.

Abstract

Myocardial infarction (MI) is a complex multifactorial cardiovascular disease. India experiences a much greater burden of MI, also suggesting an experimental increase of this burden in the future. The absolute reasons for MI are context dependent and differ with different geographical settings. Several reports indicate that SNPs that are associated with certain diseases in other populations may not be associated with Indian population. It is, therefore, important to validate the association of SNPs. Low density lipoprotein receptor related protein 8 (LRP8) gene plays central role in human lipoprotein metabolism as it facilitates the clearance of bad cholesterol LDL, VLDL from plasma and is reported to be associated with MI in the western population. However, this gene has not been studied in the South Indian population. We aim to test the role of the LRP8 gene variants correlating with the lipid profile in MI patients in South Indian population. We sequenced regions of SNPs rs10788952, rs7546246, rs2297660 and rs5174 of LRP8 in 100 MI patients and 100 age-matched controls. Our result revealed a total of 4 variations. None of the SNPs were significantly associated with MI (p>0.973). Interestingly, haplotype based association analysis showed TG and CG of rs10788952 and rs7546246 significantly associated with MI (p<0.01 and p<0.00005) and in particular, haplotype TG was positively correlated with the risk of MI, as this increased the LDL and total cholesterol level in MI patients in south Indians. Our results suggest that haplotype TG is a risk factor for MI in South Indian population.

摘要

心肌梗死(MI)是一种复杂的多因素心血管疾病。印度承受着更为沉重的心肌梗死负担,而且未来这一负担预计还会增加。心肌梗死的确切病因因地域而异。有几份报告指出,在其他人群中与某些疾病相关的单核苷酸多态性(SNP)可能与印度人群无关。因此,验证SNP的关联性很重要。低密度脂蛋白受体相关蛋白8(LRP8)基因在人体脂蛋白代谢中起核心作用,因为它有助于清除血浆中有害的胆固醇低密度脂蛋白(LDL)和极低密度脂蛋白(VLDL),据报道在西方人群中该基因与心肌梗死有关。然而,尚未在南印度人群中对该基因进行研究。我们旨在测试LRP8基因变异与南印度心肌梗死患者血脂水平的相关性。我们对100例心肌梗死患者和100例年龄匹配的对照者的LRP8基因的单核苷酸多态性rs10788952、rs7546246、rs2297660和rs5174区域进行了测序。我们的结果共发现了4种变异。没有一个SNP与心肌梗死显著相关(p>0.973)。有趣的是,基于单倍型的关联分析显示,rs10788952和rs7546246的单倍型TG和CG与心肌梗死显著相关(p<0.01和p<0.00005),特别是单倍型TG与心肌梗死风险呈正相关,因为它增加了南印度心肌梗死患者的低密度脂蛋白和总胆固醇水平。我们的结果表明,单倍型TG是南印度人群心肌梗死的一个危险因素。

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