High plasma concentrations of triglycerides (TG) and apolipoprotein C-III (ApoC-III) are well-known risk factors for cardiovascular disease. Two variants of the recently discovered APOA5, 1131 C > T and S19W, have been associated with hypertriglyceridemia, whereas their relation with coronary artery disease (CAD) remains controversial. Nine hundred and thirteen angiografically defined patients (669 CAD and 244 CAD-free) were genotyped for APOA5 −1131 C > T and S19W polymorphisms.Carriership of the APOA5 −1131 C allele was identified, by multiple linear regression models, as a significant independent predictor for both TG (standardized β-coefficient = 0.112; p = 0.010) and ApoC-III variability (standardized β-coefficient = 0.113; p = 0.013). Similarly, APOA5 19W allele carriership was a significant independent predictor for both TG (standardized β-coefficient = 0.113; p = 0.007) and ApoC-III variability (standardized β-coefficient = 0.088; p = 0.045). Despite the association with at-risk lipid profile, no significant difference was detected in the distribution of both APOA5 gene polymorphisms between subjects with or without CAD. Moreover, homozygous carriers of the APOC3 −455 C, another TG- and ApoC-III raising variant, showed a significant increased risk for CAD (OR 1.90 with 95% CI 1.002–3.62; p = 0.049; by multiple logistic regression).Different genotypes, i.e., APOA5 and APOC3 variants, may lead to similar biochemical phenotypes, namely hypertriglyceridemia, but to contrasting clinical phenotypes such as the presence of angiographically proven CAD.
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