Human Molecular Genetics, 2002, Vol. 11, No. 12 1477-1485
© 2002 Oxford University Press
Common haplotypes in five genes influence genetic variance of LDL and HDL cholesterol in the general population
1Franz Volhard Clinic, HELIOS Kliniken, Berlin, Germany, 2Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University of Berlin, Germany and 3ValiGen SA, Tour Neptune 92086 Paris-La-Defense, France
Received March 1, 2002; Accepted March 27, 2002
We studied the association between common haplotypes in six relevant lipid metabolism genes with plasma lipid levels. We selected single-nucleotide polymorphisms (SNPs) in the cholesterol ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic triglyceride lipase (HL), low-density lipoprotein cholesterol receptor (LDLR), apolipoprotein E (ApoE) and lecithin-cholesterol acyltransferase (LCAT) genes, and studied 732 individuals from 184 German families. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) were similar to those reported in other European and American populations. Haplotypes derived from SNP combinations resulted in more significance and of a higher degree than did single SNPs in the genotype–phenotype association analysis. Reduction of the polygenic variance attributable to haplotypes was estimated using variance components analysis. Under the biometrical genetic model, allelic association of haplotypes was highly significant for HDL, LDL and the LDL/HDL ratio. The residual kinship correlation was reduced accordingly. The ApoE gene had a strong effect on trait variation; however, the other genes also contributed substantially. An epistatic interaction could not be demonstrated in this sample. The data are consistent with the notion that common genetic variants influence common traits.
* To whom correspondence should be addressed at: Franz Volhard Clinic, Wiltberg Strasse 50, 13125 Berlin, Germany. Tel: +49 30 9417 2202; Fax: +49 30 9417 2206; Email: luft{at}fvk-berlin.de
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