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A more recent version of this article appeared on December 1, 2005

Papers In Press, published online ahead of print September 28, 2005
J. Lipid Res., doi:10.1194/jlr.M500040-JLR200
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Submitted on February 1, 2005
Revised on September 22, 2005
Accepted on September 26, 2005

APOC3/A5 haplotypes, lipid levels and risk of myocardial infarction in the Central Valley of Costa Rica

Edward A. Ruiz-Narvaez, Yadong Yang, Yukiko Nakanishi, Jill Kirchdorfer, and Hannia Campos

Nutrition Dept., Harvard School of Public Health, Boston, MA 02115

Corresponding Author: eruiz{at}hsph.harvard.edu

Genetic variation in the APOC3 and APOA5 genes has been associated with plasma triglyceride concentrations and may affect the risk of myocardial infarction (MI). To assess whether APOC3/A5 haplotypes are associated with risk of MI, we examined three single nucleotide polymorphisms (SNPs) in APOC3 (3238C>G, -455T>C, and -482C>T) and six SNPs in the APOA5 gene (-1131T>C, c.-3A>G, c.56C>G, IVS3+476G>A, c.553G>T, and c.1259T>C) in incident cases (n = 1703) of a first nonfatal MI matched for gender, age and area of residence with population-based controls (n = 1703). Conditional logistic regression models, adjusted for potential environmental confounders, were used for analysis. The common APOC3*222 haplotype was more frequent in cases than controls (17.4% and 13.7% respectively, p < 0.001) and associated with increased risk of MI (odds ratio (OR) = 1.27, 95% CI: 1.09, 1.48) compared to APOC3*111 wildtype haplotype. This association was independent from the APOA5 SNPs. Although the APOC3 3238G, APOA5 -1131C, APOA5 c.-3G, and APOA5 c.1259C alleles were associated with higher triglyceride plasma concentrations, these effects could not explain the associations with MI in this population. In summary, this study supports the hypothesis that haplotypes in the APOC3 gene but not APOA5 increase susceptibility to MI.


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