Objective: SNP/phenotype associations are difficult to validate. This comparative study demonstrates significant contribution of candidate genes to the variation of a complex cholesterol phenotype, measured in two general populations by a gene-based approach. Methods: Independent samples of normolipidemic subjects from two Caucasian populations (371 Swiss and 157 Germans) were selected for a case-control-study (high LDL/low HDL versus low LDL/high HDL) with SNP genotypes as independent factors. We examined locus-specific common SNPs that densely cover the genomic regions of 10 lipid genes. Results: Genotype effects were concordant in both ethnic samples, showing that APOE, ABCA1, CETP, and to a lesser degree LDLR, LIPC, and PLTP explained a substantial part of the genetic variation, whereas LPL was associated in only one sample. APOA1, LCAT, and SRB1 exerted no measurable influence. Conclusion: This comparison showed that sets of common SNPs representing candidate regions reproducibly validate significant linkage disequilibrium association with a complex metabolic trait.

Keywords:
Genotype-phenotype association, Complex polygenic trait, HDL-cholesterol, LDL-cholesterol, Lipids, Single nucleotide polymorphisms
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© 2006 S. Karger AG, Basel
2006
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