Genetic Association of the APOEAPOC1APOC4 Locus with Coronary Artery Disease

Abstract

Genome-wide association studies identified a 5' APOC1 single nucleotide polymorphism (SNP), rs4420638 (minor allele frequency (MAF)=0.18) at 19q13.2, with a CAD risk odds ratio (OR) of 1.17 (1.08-1.28) in linkage disequilibrium with apoE4 risk SNP rs429358 (r 2=0.70; OR=1.06 (0.99-1.13), MAF=0.15). Differing OR and MAF led to the hypothesis that rs4420638 risk is partially independent to rs429358. Additional SNPs not in HapMap were genotyped by sequencing, however no strong linkage existed. Genotypically associated traits include serum apoE, as determined by ELISA (rs4420638 AA: 25.5+/-4.8; AB: 44.8+/-3.1; BB: 69.9+/-3.7ug/ml; p=7.27E-07, rs429358 AA: 14.8+/-3.4; AB: 40.1+/-3.1; BB: 67.0+/-3.4ug/ml; p=1.73E-08) and LDL (linear regression rs4420638 p=0.0007; rs429358 p=0.003) but not apoC1. Haplotype analysis indicated that rs429358 risk allele confers a greater CAD risk than rs4420638: rs4420638 risk allele alone is 6% in cases and 4% in controls; rs429358 risk allele is 3% in cases and 0.3% in controls. Likelihood ratio test confirms this conclusion.