Association of DNA Polymorphism at the Apolipoprotein B-100 Gene Locus with Plasma Lipid Concentration and Coronary Artery Disease among North Indians

Abstract

The aim of this study was to investigate the association between apolipoprotein B gene polymorphisms and coronary artery disease and lipid levels in north Indians. Two hundred patients of angiographically proven atherosclerotic CAD and two hundred age and sex matched control subjects were included in the study. Serum lipids including cholesterol, triglycerides, HDL, LDL, VLDL and ApoB were analyzed. PCR based genotyping was done for ApoB 3' Hypervariable region (HVR). RFLP analysis was carried out to genotype regions carrying XBA1, EcoR1 and Msp1 restriction sites in the ApoB gene. Biochemical analysis of lipid parameters revealed that Total cholesterol, triglycerides, VLDL, LDL and ApoB were significantly high (p<0.001) in patients while HDL was found elevated in controls. ApoB 3' HVR polymorphism analysis revealed a total of 17 alleles where HVE34 (p<0.001), HVE43 (p<0.001) and HVE47 (p<0.01) were found significantly higher in CAD patient. Comparison based on three and five allelic model revealed that group of high repeat alleles (>37) were significantly (p<0.001) high in patients. RFLP analysis of three cutting sites namely Ecor1, MspI and XbaI revealed that combined genotypes E+E+M+M+X+X+ and E+E+M+M-X-X- were significantly more prevalent (p<0.002) in CAD patients. Haplotype analysis revealed that two locus E+X- and three locus E+M-X- and E-M+X- were significantly higher (p<0.01) in CAD patients. Complete four locus analysis revealed that high repeat haplotype E+M+X-/ 43 was significantly higher (p=0.0002) in patients. A significant association (p = 0.03) was also observed between the higher repeats HVE39-49 alleles and higher levels of Apo B. RFLP haplotype E+/X- also depicted significant differences for total cholesterol, triglycerides, LDL-cholesterol and Apolipoprotein B levels. The study elucidates that ApoB gene polymorphisms are associated with CAD in north Indian patients. High repeat alleles (>37) of ApoB3'HVR and E+/X- RFLP haplotype is strongly associated both with elevated lipid levels and CAD occurrence. Therefore, ApoB gene polymorphisms can be helpful in delineating the high risk group for CAD and may be of use in genetic screening of CAD patients from north India.