title: The C-480T hepatic lipase polymorphism is associated with HDL-C but not with risk of coronary heart disease.
abstract: High-density lipoprotein cholesterol (HDL-C) is a known predictor of coronary heart disease (CHD). Studies have shown that the C-480T polymorphism of the hepatic lipase (HL) gene is predictive of HDL-C; however, its observed relationship with the risk of CHD has been inconsistent. We analysed four biallelic polymorphisms in the HL gene in participants from three independent Western Australian populations. Samples were collected from two cross-sectional studies of 1111 and 4822 community-based subjects assessed for cardiovascular risk factors, and a third sample of 556 subjects with physician-diagnosed CHD. Genotypes were tested for association with plasma lipids and the risk of CHD. All polymorphisms were highly correlated (D' > 0.97, r(2) > 0.90); therefore, only C-480T was analysed. The -480T allele was significantly associated with an increase in HDL-C of between 0.08 and 0.16 mmol/l in all three populations (p < 0.001). No associations with other lipids were observed, nor was an association with CHD in a case-control study of males. The TT genotype was however associated with decreased risk of myocardial infarction among cases (odds ratio = 0.39, 95% confidence interval = 0.19-0.78, p = 0.008). These findings replicate those of previous studies in three independent populations and suggest that the genetic determinants of CHD are complex and cannot be entirely explained through intermediate phenotypes.
authors.affiliation: Laboratory for Genetic Epidemiology, Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Nedlands, Perth, Western Australia. pmccask@cyllene.uwa.edu.au
authors.forename: P A
authors.initials: PA
authors.lastname: McCaskie
authors.forename: G
authors.initials: G
authors.lastname: Cadby
authors.forename: J
authors.initials: J
authors.lastname: Hung
authors.forename: B M
authors.initials: BM
authors.lastname: McQuillan
authors.forename: C M L
authors.initials: CM
authors.lastname: Chapman
authors.forename: K W
authors.initials: KW
authors.lastname: Carter
authors.forename: P L
authors.initials: PL
authors.lastname: Thompson
authors.forename: L J
authors.initials: LJ
authors.lastname: Palmer
authors.forename: J P
authors.initials: JP
authors.lastname: Beilby
mesh_terms: D000328:Adult; D000368:Aged; D008076:Cholesterol, HDL / Q000235:genetics*; D003327:Coronary Disease / Q000209:etiology / Q000235:genetics*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D008076:Cholesterol, HDL; C504173:LIPC protein, human; D008049:Lipase