title: C-514T polymorphism in hepatic lipase gene promoter is associated with elevated triglyceride levels and decreasing insulin sensitivity in nondiabetic Japanese subjects.
abstract: Hepatic lipase (HL) is synthesized in the liver and hydrolyses triglyceride and phospholipids. C-514T polymorphism in HL gene promoter was reported to associate with hepatic lipase activity and plasma lipid levels. We examined whether C-514T polymorphism affects glucose metabolism beyond its effect on plasma lipid levels in nondiabetic Japanese subjects. Gene frequencies of C/C homozygote, C/T heterozygote and T/T homozygote were 18, 51 and 31%, respectively. The allelic frequencies of C and T were 44 and 56%, respectively. T allele frequency was much higher than in Caucasian subjects. Moreover, -514T allele carriers had higher levels of triglyceride (P=0.027), fasting insulin (P=0.016) and HOMA-IR (P=0.033) than non-carriers. In contrast to some former studies, -514T allele affected triglyceride levels and insulin sensitivity. Taken together, HL gene might be one of the important susceptibility genes of type 2 diabetes and the high incidence of type 2 diabetes could be explained by high frequency of -514T allele in the Japanese population. Moreover, since HL and adiponectin showed an additive effect on insulin sensitivity, these genetic variations can be independently associated with insulin sensitivity.
authors.affiliation: Department of Laboratory Medicine, Mie University School of Medicine, Tsu, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Yabu
authors.forename: Katsura
authors.initials: K
authors.lastname: Noma
authors.forename: Kaname
authors.initials: K
authors.lastname: Nakatani
authors.forename: Junji
authors.initials: J
authors.lastname: Nishioka
authors.forename: Mina
authors.initials: M
authors.lastname: Suematsu
authors.forename: Akira
authors.initials: A
authors.lastname: Katsuki
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Hori
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yano
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Sumida
authors.forename: Hideo
authors.initials: H
authors.lastname: Wada
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nobori
mesh_terms: D052242:Adiponectin; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007564:Japan; D008049:Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*
chemical_list: D052242:Adiponectin; D036341:Intercellular Signaling Peptides and Proteins; C504173:LIPC protein, human; D014280:Triglycerides; D008049:Lipase