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Journal of Lipid Research, Vol. 46, 2605-2613, December 2005 APOC3/A5 haplotypes, lipid levels, and risk of myocardial infarction in the Central Valley of Costa Rica
* Department of Nutrition, Harvard School of Public Health, Boston, MA Published, JLR Papers in Press, September 28, 2005. DOI 10.1194/jlr.M500040-JLR200
1 To whom correspondence should be addressed. e-mail: hcampos{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 = 1,703) of a first nonfatal MI matched for gender, age, and area of residence with population-based controls (n = 1,703). Conditional logistic regression models, adjusted for potential environmental confounders, were used for analysis. The common APOC3*222 haplotype was more frequent in cases than in controls (17.4% and 13.7%, respectively, P < 0.001) and was associated with increased risk of MI [odds ratio (OR) = 1.27; 95% confidence interval (95% CI), 1.09, 1.48] compared with APOC3*111 wild-type haplotype. This association was independent of 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 in the APOA5 gene increase susceptibility to MI.
Abbreviations: apoC-III, apolipoprotein C-III; ASA, allele-specific assay; CHD, coronary heart disease; IRE, insulin response element; LD, linkage disequilibrium; MI, myocardial infarction; ROR Supplementary key words apolipoprotein genetics epidemiology cardiovascular disease risk factors
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