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Papers In Press, published online ahead of print November 1, 2004
J. Lipid Res., doi:10.1194/jlr.M400192-JLR200
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Journal of Lipid Research, Vol. 45, 2096-2105, November 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology
Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study
* Nutrition and Genomics Laboratory, Jean Mayer–United States Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA
School of Public Health and School of Medicine, Boston University, Boston, MA
Genetic and Molecular Epidemiology Unit, University of Valencia, Valencia, Spain
1 To whom correspondence should be addressed. e-mail: chao.lai{at}tufts.edu
Several polymorphisms in the APOA5 gene have been associated with increased plasma triglyceride (TG) concentrations. However, associations between APOA5 and lipoprotein subclasses, remnant-like particles (RLPs), and cardiovascular disease (CVD) risk have been less explored. We investigated associations of five APOA5 single-nucleotide polymorphisms (SNPs; –1131T>C, –3A>G, 56C>G IVS3+ 476G>A, and 1259T>C) with lipoprotein subfractions and CVD risk in 1,129 men and 1,262 women participating in the Framingham Heart Study. Except for the 56C>G SNP, the other SNPs were in significant linkage disequilibria, resulting in three haplotypes (11111, 22122, and 11211) representing 98% of the population. SNP analyses revealed that the –1131T>C and 56C>G SNPs were significantly associated with higher plasma TG concentrations in both men and women. For RLP and lipoprotein subclasses, we observed gender-specific association for the –1131T>C and 56C>G SNPs. Female carriers of the –1131C allele had higher RLP concentrations, whereas in males, significant associations for RLPs were observed for the 56G allele. Moreover, haplotype analyses confirmed these findings and revealed that the 22122 and 11211 haplotypes exhibited different associations with HDL cholesterol concentrations.
In women, the –1131C allele was associated with a higher hazard ratio for CVD (1.85; 95% confidence interval, 1.03–3.34; P = 0.04), in agreement with the association of this SNP with higher RLPs.
Supplementary key words apolipoprotein A-V • triglycerides • cardiovascular disease risk • haplotype • remnant-like particles
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