ApoC-III gene polymorphisms and risk of coronary artery disease

Oliviero Olivieri, Chiara Stranieri, Antonella Bassi, Barbara Zaia, Domenico Girelli, Francesca Pizzolo, Elisabetta Trabetti, Suzanne Cheng, Michael A. Grow, Pier Franco Pignatti, Roberto Corrocher
2002 Journal of Lipid Research  
Several polymorphisms in the apolipoprotein C-III (apoC-III) gene have been associated with hypertriglyceridemia, but the link with coronary artery disease risk is still controversial. In particular, apoC-III promoter sequence variants in the insulin responsive element (IRE), constitutively resistant to downregulation by insulin, have never been investigated in this connection. We studied a total of 800 patients, 549 of whom had angiographically documented coronary atherosclerosis, whereas 251
more » ... ad normal coronary arteriograms. We measured plasma lipids, insulin, apoA-I, apoB, and apoC-III and assessed three polymorphisms in the apoC-III gene, namely, T-455C in the IRE promoter region, C1100T in exon 3, and Sst1 polymorphic site (S1/S2) in the 3 untranslated region. Each variant influenced triglyceride levels, but only the T-455C (in homozygosity) and S2 alleles influenced apoC-III levels. In coronary artery disease (CAD) patients, 18.6% were homozygous for the ؊ 455C variant compared with only 9.2% in CAD-free group ( P Ͻ 0.001). In logistic regression models, homozygosity for ؊ 455C variant was associated with a significantly increased risk of CAD (OR ‫؍‬ 2.5 and 2.18 for unadjusted and adjusted models, respectively) suggesting that it represents an independent genetic susceptibility factor for CAD. -
doi:10.1194/jlr.m200145-jlr200 pmid:12235176 fatcat:yb4qxumtbbagjg62u5gphizqbq