Impact of APOA5/A4/C3 genetic polymorphisms on lipid variables and cardiovascular disease risk in French men.

Objective: The goal of the present study was to assess the impact of 4 single nucleotide polymorphisms (SNPs) of APOA5/A4/C3 gene cluster on lipid levels and coronary heart disease (CHD) risk in French men.

Methods: A total of 442 men with CHD were recruited from the university hospital and compared to 475 men free of CHD from the population of the same geographical area. The APOA5 S19W, APOA5 -l2,238T>C, APOA4 T347S and APOC3 -482C>T SNPs were examined.

Results: The APOA5 S19W polymorphism was associated with plasma triglyceride levels. In multivariate logistic regression analyses the odds ratio (OR [95% Cl]) of hypertriglyceridemia (3rd vs. 1st tertile of triglyceride distribution) was 3.60 [1.38-9.42] in control subjects bearing at least one APOA5 19W variant. Haplotype analyses revealed a significant association between the 2111 haplotype and high triglyceride levels (+1.94 +/- 0.63 vs. 0.74 +/- 0.36 mmol/l for the 1111 haplotype p < 0.002). There was, in contrast, no significant difference in SNP distribution between CHD patients and controls. The age-adjusted OR of CHD were 1.46 [0.96-2.23], 0.79 [0.60-1.05], 0.91 [0.69-1.21] and 0.91 [0.69-l.22] in carriers of the APOA5 19W, APOA5 -12,238C, APOA4 347S and APOC3 -482T variants, respectively. There was also no significant difference in APOA5/A4/C3 haplotype distribution in patients and controls.

Conclusion: The APOA5 19W variant is associated with increased plasma triglycerides. However, there is no evidence that APOA5 S19W, -12,238T > C, APOA4 T347S and APCC3 -482C > T SNPs are major risk factors of CHD in French men.