Journal of Lipid Research (Sep 2002)

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

Journal volume & issue
Vol. 43, no. 9
pp. 1450 – 1457

Abstract

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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 had 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 < 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.

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