Journal of Molecular Medicine

, Volume 84, Issue 7, pp 561–572

The contribution of individual and pairwise combinations of SNPs in the APOA1 and APOC3 genes to interindividual HDL-C variability

Authors

  • C. M. Brown
    • Department of Human GeneticsUniversity of Michigan
  • T. J. Rea
    • Department of Human GeneticsUniversity of Michigan
  • S. C. Hamon
    • Laboratory of Statistical GeneticsRockefeller University
  • J. E. Hixson
    • Human Genetics CenterUniversity of Texas Health Science Center
  • E. Boerwinkle
    • Human Genetics CenterUniversity of Texas Health Science Center
  • A. G. Clark
    • Department of Molecular Biology and GeneticsCornell University
    • Department of Human GeneticsUniversity of Michigan
Original Article

DOI: 10.1007/s00109-005-0037-x

Cite this article as:
Brown, C.M., Rea, T.J., Hamon, S.C. et al. J Mol Med (2006) 84: 561. doi:10.1007/s00109-005-0037-x

Abstract

Apolipoproteins (apo) A-I and C-III are components of high-density lipoprotein-cholesterol (HDL-C), a quantitative trait negatively correlated with risk of cardiovascular disease (CVD). We analyzed the contribution of individual and pairwise combinations of single nucleotide polymorphisms (SNPs) in the APOA1/APOC3 genes to HDL-C variability to evaluate (1) consistency of published single-SNP studies with our single-SNP analyses; (2) consistency of single-SNP and two-SNP phenotype–genotype relationships across race-, gender-, and geographical location-dependent contexts; and (3) the contribution of single SNPs and pairs of SNPs to variability beyond that explained by plasma apo A-I concentration. We analyzed 45 SNPs in 3,831 young African–American (N=1,858) and European–American (N=1,973) females and males ascertained by the Coronary Artery Risk Development in Young Adults (CARDIA) study. We found three SNPs that significantly impact HDL-C variability in both the literature and the CARDIA sample. Single-SNP analyses identified only one of five significant HDL-C SNP genotype relationships in the CARDIA study that was consistent across all race-, gender-, and geographical location-dependent contexts. The other four were consistent across geographical locations for a particular race–gender context. The portion of total phenotypic variance explained by single-SNP genotypes and genotypes defined by pairs of SNPs was less than 3%, an amount that is miniscule compared to the contribution explained by variability in plasma apo A-I concentration. Our findings illustrate the impact of context-dependence on SNP selection for prediction of CVD risk factor variability.

Keywords

APOA1 geneAPOC3 geneHigh-density lipoprotein-cholesterolCardiovascular disease

Supplementary material

Copyright information

© Springer-Verlag 2006