title: DNA variants at the LPL gene locus associate with angiographically defined severity of atherosclerosis and serum lipoprotein levels in a Welsh population.
abstract: Coronary artery disease (CAD) patients (n = 235), comprising minimal (CAD-, n = 124) and severe (CAD+, n = 111) CAD, were recruited on the basis of their angiographic scores. Male control subjects (n = 123) were selected randomly from the Caerphilly Heart Study cohort. Subjects were genotyped for the Ser447-Ter mutation and HindIII/Pvu II restriction fragment length polymorphisms of the lipoprotein lipase gene and investigated for associations with severity and development of CAD and lipid and lipoprotein levels. The Ser447-Ter mutation showed no significant associations with CAD or dyslipidemia but was related to favorable lipid and lipoprotein profiles. The H2H2 genotype (P < .05) and H2 allele (P = .05) were significantly more frequent in CAD+ versus CAD- and control subjects versus CAD-. H2H2 subjects, among the entire male cohort, had significantly higher levels of apolipoprotein B (P = .0002), total cholesterol (P < .004), and triglycerides (P < .04) than alternative genotypes. P2P2 associated with significantly lower high-density lipoprotein cholesterol levels (P < .01). The H2 allele had most significant associations with raised apolipoprotein B levels compared with other biochemical parameters. Our data suggest that the H2 allele may be a linkage marker for an etiologic mutation for dyslipidemia and the severity and development of atherosclerosis; this is not the Ser447-Ter mutation.
authors.affiliation: Department of Human Genetics and Metabolism, St. Bartholomew's Hospital Medical College, London, UK.
authors.forename: R K
authors.initials: RK
authors.lastname: Mattu
authors.forename: E W
authors.initials: EW
authors.lastname: Needham
authors.forename: R
authors.initials: R
authors.lastname: Morgan
authors.forename: A
authors.initials: A
authors.lastname: Rees
authors.forename: A K
authors.initials: AK
authors.lastname: Hackshaw
authors.forename: J
authors.initials: J
authors.lastname: Stocks
authors.forename: P C
authors.initials: PC
authors.lastname: Elwood
authors.forename: D J
authors.initials: DJ
authors.lastname: Galton
mesh_terms: D000483:Alleles; D001059:Apoproteins / Q000097:blood; D001483:Base Sequence; D015415:Biomarkers; D002784:Cholesterol / Q000097:blood*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005260:Female; D005796:Genes; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D014280:Triglycerides / Q000097:blood
chemical_list: D001059:Apoproteins; D015415:Biomarkers; D017931:DNA Primers; D014280:Triglycerides; D004247:DNA; D002784:Cholesterol; D008071:Lipoprotein Lipase