C-514T polymorphism in hepatic lipase gene promoter is associated with elevated triglyceride levels and decreasing insulin sensitivity in nondiabetic Japanese subjects.

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.