Abstract 1638: Synergistic Effects of the Apolipoprotein E E2/E3/E4, the Apolipoprotein C3 −482 C>T, and the Cholesteryl Ester Transfer Protein TaqIB Polymorphisms on the Risk of Coronary Artery Disease
Background: The genes encoding for apolipoprotein E (apoE), for apolipoprotein C3 (apoC3), and for cholesteryl ester transfer protein (CETP) play key roles in lipid metabolism. Their frequent variants APOE E3/E4/E2, APOC3 −482 C>T, and CETP Taq1B B1>B2 are associated with atherogenic dyslipidemia and - in some studies - with the risk of coronary artery disease (CAD). A potential synergistic effect of these polymorphisms on the risk of CAD has not been investigated yet.
Methods: We analysed the APOE E3/E4/E2, the APOC3 −482 C>T, and the CETP TaqIB polymorphisms by 5′nuclease assay in 557 patients undergoing coronary angiography for the evaluation of established or suspected stable CAD. Significant CAD was defined as the presence of coronary stenoses with narrowings of at least ≥50%.
Results: From our patients, 129 carried the APOE E4 allele, 278 the APOC3 −482T allele and 196 the CETP B1B1 genotype. After multivariate adjustment, presence of the APOE E4 allele proved significantly associated with an increased risk of significant CAD (1.589 [95% CI 1.013–2.491]; p =0.044); the respective odds ratios associated with the APOC3 −482T allele and the CETP B1B1 genotype were 1.170 [0.813–1.686]; p =0.398 and 1.453 [0.985–2.142]; p =0.059, respectively. Importantly, the risk of significant CAD was strongly increased in patients with more than one of the analysed genetic variants: adjusted odds ratios were 1.831 [1.113–3.013]; p =0.017 for patients with both the APOE E4 allele and the CETP B1B1 genotype, 1.983 [1.017–3.868]; p =0.045 for patients with both the APOE E4 and the APOC3 −482T alleles, 2.498 [1.474 – 4.231]; p =0.001 for patients with both the CETP B1B1 genotype and the APOC3 −482T allele, and 4.491 [1.222–16.499]; p =0.028 for patients with all three variants.
Conclusions: There are strong synergistic effects of the APOE E3/E4/E2, the APOC3 −482 C>T, and the CETP TaqIB polymorphisms on the risk of angiographically diagnosed CAD.