title: Effects of hepatic lipase gene promoter nucleotide variations on serum HDL cholesterol concentration in the general Japanese population.
abstract: Genetic factors may play a major role in determining serum high-density lipoprotein (HDL) cholesterol (HDL-C) levels in the general population. Cholesteryl ester transfer protein (CETP) is a strong genetic factor as a determinant of HDL-C levels in Japanese, whereas hepatic lipase (HL) plays a predominant role in Caucasian populations. We investigated the effects of HL gene promoter polymorphisms on HDL-C levels in a general population of Japanese men (n = 299). An HL promoter polymorphism of -514C/T explained a considerable variance of HDL-C (2.9%), as compared with CETP mutations of D442G and IVS14 + 1G > A (3.6% and 1.9%). HL promoter variation of the -514C/C genotype, reported to have high HL activity, had significant effects on decreasing HDL-C levels (-3.8mg/dl), but -514T allele carriers had a weak effect on increasing HDL-C levels. The frequency of the -514T allele was three times higher (0.50) in the Japanese than in Caucasian populations (0.15-0.19). Thus, the higher frequency of the HL -514T allele, along with CETP gene mutations, could explain about 9% of phenotypic variability of HDL-C. These genetic attributes may be among the many factors that contribute to the relatively higher serum HDL-C levels in Japanese subjects.
authors.affiliation: The Second Department of Internal Medicine, School of Medicine, Kanazawa University, Japan. inazua@mhs.mp.kanazawa-u.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Inazu
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Y
authors.initials: Y
authors.lastname: Terada
authors.forename: H
authors.initials: H
authors.lastname: Mabuchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics* / Q000494:pharmacology; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood* / Q000187:drug effects; D004252:DNA Mutational Analysis; D005838:Genotype; D006023:Glycoproteins; D006801:Humans; D007564:Japan; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012044:Regression Analysis
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D008049:Lipase