Gene Polymorphism and Coronary Risk Factors in Indian Population

Abstract

Asian Indians who have settled overseas and those in urban India have increased risk of coronary events. Reasons for this increased risk are thought to be genetic but are yet unclear. Advances in molecular cardiology have revealed a number of single nucleotide polymorphisms associated with atherosclerosis. In this review, gene polymorphisms that have been associated with coronary diseases among Indians are discussed. Topics include the genes involved in hyperlipidemia, hypertension, and homocysteine. Mutations in the low-density lipoprotein receptor (LDLR) gene resulting in familial hypercholesterolemia have strong association with premature atherosclerosis. Common polymorphism of the apolipoproteins (apo) B-100 and E genes have been associated with variation in lipid and lipoprotein levels. Recently identified polymorphisms in the apoC3 (T-455C, C-482T), and cholesteryl ester transfer protein (CETP) (B1/B2 allele) genes are associated with increased triglycerides and reduced high-density lipoprotein (HDL)-levels, a feature now also common among Asian Indians. Angiotensin-converting enzyme-deletion (DD) polymorphism has been shown to influence beta-blocker therapy in heart failure. Mutations in methylenetetrahydrofolate reductase (C667T), cystathionine beta-synthase (T833C), and methionine synthase (A2756G) genes cause hyperhomocysteinemia, an independent risk factor for atherothrombosis. As the genetics of atherosclerosis continues to evolve, these factors along with the newer emerging factors may become a part of the routine assessment, aiding prediction of future coronary events.

Effect of Hepatic Lipase −514C→T Polymorphism and Its Interactions With Apolipoprotein C3 −482C→T and Apolipoprotein E Exon 4 Polymorphisms on the Risk of Nephropathy in Chinese Type 2 Diabetic Patients

“…It can increase triglycerides by inhibiting lipases (26). Insulin reduces apoC3 expression and induces HL expression (14,27) to help remove postprandial triglycerides (26).…”

“…Insulin reduces apoC3 expression and induces HL expression (14,27) to help remove postprandial triglycerides (26). The Ϫ482C3 T polymorphism lies in an apoC3 gene promoter insulin response element, and functional studies have demonstrated that the Ϫ482T allele reduces the inhibitory effect of insulin on apoC3 expression (26).…”

The Allele Frequencies of Three Polymorphisms in Genes Involved in Homocysteine Metabolism in a Group of Unrelated Healthy Singaporeans

“…At the MS gene, an A to G transition at nucleotide 2756 (A2756G), which results in the substitution of glycine for aspartic acid at amino acid position 919 (D919G), has been described [4]. In Indian [5] and Korean [6] populations, the 2756G allele was found to be associated with increased Hcy levels. Finally at the MTHFR gene, a common C to T transition at nucleotide 677 (C677T), which leads to the substitution of valine for alanine, has been reported to impair the enzymatic activity of MTHFR [7], and the homozygous form of the 677T allele (T/T genotype) is therefore associated with higher Hcy concentrations than the other two genotypes among major Asian populations including Japanese [8,9], Koreans [6], and Chinese [10,11].…”

Chromosome 9p21 polymorphism is associated with myocardial infarction but not with clinical outcome in Han Chinese

“…It is widely accepted that genetic variation is important for the pathogenesis of coronary artery disease (CAD), myocardial infarction (MI) and clinical outcome (1,2). Although numerous candidate genes have been implicated in the development and progression of atherosclerosis, the genes that are responsible remain largely unknown.…”