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载脂蛋白基因簇上的遗传变异会影响甘油三酯水平,并增加印度人患冠状动脉疾病的风险。

Genetic variants on apolipoprotein gene cluster influence triglycerides with a risk of coronary artery disease among Indians.

作者信息

AshokKumar Manickaraj, Subhashini Navaneethan Gnana Veera, SaiBabu Ramineni, Ramesh Arabandi, Cherian Kotturathu Mammen, Emmanuel Cyril

机构信息

International Centre for Cardiothoracic and Vascular Diseases, Frontier Lifeline, Chennai, India.

出版信息

Mol Biol Rep. 2010 Jan;37(1):521-7. doi: 10.1007/s11033-009-9728-7. Epub 2009 Aug 22.

DOI:10.1007/s11033-009-9728-7
PMID:19701693
Abstract

Apolipoprotein C3 and apolipoprotien A5 are proteins coded from the APOA1/C3/A4/A5 gene cluster. Sst I polymorphism on apolipoprotein C3 and -1131C polymorphism of apolipoprotien A5 are key variants involved in triglyceride metabolism and cause a significant cardio-metabolic risk. Here, we have evaluated these two variants for their roles in coronary artery disease in patients of the Indian population. The apolipoprotein gene cluster variants were analysed in 416 angiographically determined coronary artery disease patients and matched 416 controls using polymerase chain reaction-restriction fragment length polymorphism. The characteristics of the study subjects were analyzed statistically for their association with the polymorphisms. The alleles were combined as haplotypes and their combined risks were evaluated. The minor allele genotypes of both apolipoprotein C3 (S2) and apolipoprotien A5 (C) had a significant risk for coronary artery disease. The S2 allele genotyped patients had a significantly increased triglyceride level (P < 0.001) and increased triglycerides were observed among both patient and control CC genotype carriers. We identified the haplotype S2/C with a significant increased risk (P < 0.001) to coronary artery disease with increased levels of circulating triglycerides compared to other haplotypes in patients. We conclude that the variants on apolipoprotein C3 and apolipoprotien A5 modulate serum triglyceride levels and increase the risk of coronary artery disease.

摘要

载脂蛋白C3和载脂蛋白A5是由APOA1/C3/A4/A5基因簇编码的蛋白质。载脂蛋白C3上的Sst I多态性和载脂蛋白A5的-1131C多态性是参与甘油三酯代谢的关键变异,会导致显著的心脏代谢风险。在此,我们评估了这两种变异在印度人群冠状动脉疾病中的作用。采用聚合酶链反应-限制性片段长度多态性方法,对416例经血管造影确诊的冠状动脉疾病患者和416例匹配的对照者进行载脂蛋白基因簇变异分析。对研究对象的特征与多态性的相关性进行统计学分析。将等位基因组合成单倍型并评估其综合风险。载脂蛋白C3(S2)和载脂蛋白A5(C)的次要等位基因基因型均具有显著的冠状动脉疾病风险。携带S2等位基因的患者甘油三酯水平显著升高(P < 0.001),并且在患者和对照的CC基因型携带者中均观察到甘油三酯升高。我们鉴定出单倍型S2/C与冠状动脉疾病风险显著增加(P < 0.001)相关,与患者中的其他单倍型相比,其循环甘油三酯水平升高。我们得出结论,载脂蛋白C3和载脂蛋白A5的变异调节血清甘油三酯水平并增加冠状动脉疾病风险。

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本文引用的文献

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Study of apolipoproteinc3 Sstl polymorphism in healthy volunteers from Northern India.印度北部健康志愿者载脂蛋白C3 Sstl基因多态性研究。
Indian J Clin Biochem. 2003 Jul;18(2):34-8. doi: 10.1007/BF02867365.
2
The -1131T>C SNP of the APOA5 gene modulates response to fenofibrate treatment in patients with the metabolic syndrome: a postprandial study.载脂蛋白A5基因-1131T>C单核苷酸多态性对代谢综合征患者非诺贝特治疗反应的影响:一项餐后研究
Atherosclerosis. 2009 Sep;206(1):148-52. doi: 10.1016/j.atherosclerosis.2009.02.024. Epub 2009 Mar 11.
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Apolipoprotein A5 gene -1131T/C polymorphism is associated with the risk of metabolic syndrome in ethnic Chinese in Taiwan.
勘误:载脂蛋白C3基因多态性定量评估上遗留的问号。
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Distinct Patterns of Association of Variants at 11q23.3 Chromosomal Region with Coronary Artery Disease and Dyslipidemia in the Population of Andhra Pradesh, India.印度安得拉邦人群中11q23.3染色体区域变异与冠状动脉疾病和血脂异常的独特关联模式
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Association of APOA5 T1131C polymorphism and risk of coronary artery disease.APOA5基因T1131C多态性与冠状动脉疾病风险的关联。
Int J Clin Exp Med. 2015 Jun 15;8(6):8986-94. eCollection 2015.
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Genetic studies on the APOA1-C3-A5 gene cluster in Asian Indians with premature coronary artery disease.对患有早发性冠状动脉疾病的亚洲印度人的载脂蛋白A1-C3-A5基因簇的遗传学研究。
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Epidemiology and causation of coronary heart disease and stroke in India.印度冠心病和中风的流行病学与病因
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Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans.与欧洲人相比,印度浦那人群中载脂蛋白A5(APOA5)基因的甘油三酯相关多态性具有非常不同的等位基因频率。
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The APOA1/C3/A4/A5 gene cluster, lipid metabolism and cardiovascular disease risk.载脂蛋白A1/C3/A4/A5基因簇、脂质代谢与心血管疾病风险
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