title: The lipoprotein subfraction profile: heritability and identification of quantitative trait loci.
abstract: The HDL and LDL subclass profile is an emerging cardiovascular risk factor. Yet, the biological and genetic mechanisms controlling the lipoprotein subclass distribution are unclear. Therefore, we aimed 1) to determine the heritability of the entire spectrum of LDL and HDL subclass features and 2) to identify gene loci influencing the lipoprotein subfraction pattern. Using NMR spectroscopy, we analyzed the lipoprotein subclass distribution in 1,275 coronary artery disease patients derived from the Regensburg Myocardial Infarction Family Study. We calculated heritabilities, performed a microsatellite genome scan, and calculated linkage. HDL and LDL subclass profiles showed heritabilities ranging from 23% to 67% (all P < 10(-3)) of traits using univariate calculation. After multivariate adjustment, we found heritabilities of 27-48% (all P < 0.05) for HDL and 21-44% for LDL traits. The linkage analysis revealed a significant logarithm of the odds (LOD) score (3.3) for HDL particle concentration on chromosome 18 and a highly suggestive signal for HDL particle size on chromosome 12 (2.9). After multivariate adjustment, we found a significant maximum LOD score of 3.7 for HDL size. Our study is the first to analyze heritability and linkage for the entire spectrum of LDL and HDL subclass features. Our findings may lead to the identification of genes controlling the lipoprotein subclass distribution.
authors.affiliation: Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Regensburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kaess
authors.forename: Marcus
authors.initials: M
authors.lastname: Fischer
authors.forename: Andrea
authors.initials: A
authors.lastname: Baessler
authors.forename: Klaus
authors.initials: K
authors.lastname: Stark
authors.forename: Fritz
authors.initials: F
authors.lastname: Huber
authors.forename: Werner
authors.initials: W
authors.lastname: Kremer
authors.forename: Hans Robert
authors.initials: HR
authors.lastname: Kalbitzer
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.forename: Guenter
authors.initials: G
authors.lastname: Riegger
authors.forename: Christian
authors.initials: C
authors.lastname: Hengstenberg
mesh_terms: D005190:Family; D005260:Female; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008074:Lipoproteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D040641:Quantitative Trait Loci / Q000235:genetics*; D019655:Quantitative Trait, Heritable
chemical_list: D008074:Lipoproteins