A combination of proatherogenic single-nucleotide polymorphisms is associated with increased risk of coronary artery disease and myocardial infarction in Asian Indians.
Common single-nucleotide polymorphisms (SNPs) in genes of lipid metabolism modestly influence plasma low-density lipoprotein cholesterol (LDL-C) and risk of coronary artery disease (CAD). We evaluated a panel of LDL-C-modulating SNPs for potential association with risk of CAD in Asian Indians. Fifteen SNPs of CETP, ABCB1, APOAI, CYP7A1, and HMGCR genes were genotyped in 265 CAD patients and 150 controls of North Indian origin. A proatherogenic genotype score was formulated based on number of alleles associated with LDL-C and was evaluated for association with risk of CAD. We observed 12 SNPs from CETP, APOAI, ABCB1, CYP7A1, and HMGCR genes to be associated with baseline LDL-C and high-density lipoprotein cholesterol levels and increased risk of CAD (p < 0.05). Co-occurrence of three or more risk alleles (proartherogenic genotype score >or=3) was associated with increased risk of CAD and myocardial infarction. Analysis of epistatic interactions revealed CETPTaqIB1B1/405II/APOAI-75GA to be best model of CAD risk prediction in our population. Our study highlights synergistic association of multiple SNPs of lipid pathway with LDL-C levels and risk of CAD, and indicates that co-occurrence of proatherogenic risk alleles may provide incremental information about CAD risk beyond lipid concentrations.
Poduri
Aruna
A
Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
Khullar
Madhu
M
Bahl
Ajay
A
Sharma
Yash Paul
YP
Talwar
Kewal K
KK
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D000483:Alleles; D016632:Apolipoprotein A-I / Q000235:genetics; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D007194:India; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016632:Apolipoprotein A-I; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase