title: Common haplotypes in five genes influence genetic variance of LDL and HDL cholesterol in the general population.
abstract: 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.
authors.affiliation: Franz Volhard Clinic, HELIOS Kliniken, Berlin, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Knoblauch
authors.forename: Anja
authors.initials: A
authors.lastname: Bauerfeind
authors.forename: Christine
authors.initials: C
authors.lastname: Krähenbühl
authors.forename: Aurelie
authors.initials: A
authors.lastname: Daury
authors.forename: Klaus
authors.initials: K
authors.lastname: Rohde
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bejanin
authors.forename: Laurent
authors.initials: L
authors.lastname: Essioux
authors.forename: Herbert
authors.initials: H
authors.lastname: Schuster
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.forename: Jens Georg
authors.initials: JG
authors.lastname: Reich
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D005260:Female; D014644:Genetic Variation; D006023:Glycoproteins; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001057:Apolipoproteins E; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D008049:Lipase; D008071:Lipoprotein Lipase