DNA VARIANTS AT THE LPL GENE LOCUS ASSOCIATE WITH ANGIOGRAPHICALLY DEFINED SEVERITY OF ATHEROSCLEROSIS AND SERUM-LIPOPROTEIN LEVELS IN A WELSH POPULATION

Coronary artery disease (CAD) patients (n=235), comprising minimal (CA D(-), n=124) and severe (CAD(+), n=111) CAD, were recruited on the bas is of their angiographic scores. Male control subjects (n=123) were se lected randomly from the Caerphilly Heart Study cohort. Subjects were genotyped for the Ser(447)-Ter mutation and HindIII/Pvu II restriction fragment length polymorphisms of the lipoprotein lipase gene and inve stigated for associations with severity and development of CAD and lip id and lipoprotein levels. The Ser(447)-Ter mutation showed no signifi cant associations with CAD or dyslipidemia but was related to favorabl e lipid and lipoprotein profiles. The H2H2 genotype (P<.05) and H2 all ele (P=.05) were significantly more frequent in CAD(+) versus CAD(-) a nd control subjects versus CAD(-). H2H2 subjects, among the entire mal e cohort, had significantly higher levels of apolipoprotein B (P=.0002 ), total cholesterol (P<.004), and triglycerides (P<.04) than alternat ive genotypes. P2P2 associated with significantly lower high-density l ipoprotein cholesterol levels (P<.01). The H2 allele had most signific ant associations with raised apolipoprotein B levels compared with oth er biochemical parameters. Our data suggest that the H2 allele may be a linkage marker for an etiologic mutation for dyslipidemia and the se verity and development of atherosclerosis; this is not the Ser(447)-Te r mutation.