ApoC-III gene polymorphisms and risk of coronary artery disease.
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.
Olivieri
Oliviero
O
Unit of Internal Medicine, Institute of Clinical Chemistry, University of Verona, Verona, Italy. oliviero.olivieri@univr.it
Stranieri
Chiara
C
Bassi
Antonella
A
Zaia
Barbara
B
Girelli
Domenico
D
Pizzolo
Francesca
F
Trabetti
Elisabetta
E
Cheng
Suzanne
S
Grow
Michael A
MA
Pignatti
Pier Franco
PF
Corrocher
Roberto
R
D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B / Q000097:blood; D001056:Apolipoproteins C / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic
D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001055:Apolipoproteins B; D001056:Apolipoproteins C; D015415:Biomarkers; D007328:Insulin