Effects of hepatic lipase gene promoter nucleotide variations on serum HDLcholesterol concentration in the general Japanese population

Genetic factors may play a major role in determining serum high-density lip oprotein (HDL) cholesterol (HDL-C) levels in the general population. Choles teryl ester transfer protein (CETP) is a strong genetic factor as a determi nant of HDL-C levels in Japanese, whereas hepatic lipase (HL) plays a predo minant role in Caucasian populations. We investigated the effects of HL gen e promoter polymorphisms on HDL-C levels in a general population of Japanes e men (n = 299). An HL promoter polymorphism of -514C/T explained a conside rable variance of HDL-C (2.9%), as compared with CETP mutations of D442G an d IVS14 + 1G > A (3.6% and 1.9%). HL promoter variation of the -514C/C geno type, reported to have high HL activity, had significant effects on decreas ing HDL-C levels (-3.8 mg/dl), but -514T allele carriers had a weak effect on increasing HT)L-C levels. The frequency of the -514T allele was three ti mes 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 m utations, could explain about 9% of phenotypic variability of HDL-C. These genetic attributes may be among the many factors that contribute to the rel atively higher serum HDL-C levels in Japanese subjects.