Association of the C-514T polymorphism in the hepatic lipase gene with variations in lipoprotein subclass profiles - The Framingham Offspring Study

Hepatic lipase is involved in the metabolism of several lipoproteins and ha s a key role in reverse cholesterol transport. A common C-to-T substitution at position -514 of the hepatic lipase promoter has been associated with v ariations in plasma high density lipoprotein cholesterol (HDL-C) levels and hepatic lipase activity. The aim of the current study was to investigate t he association of this polymorphism to lipoprotein levels in a population-b ased sample of 1314 male and 1353 female Framingham Offspring Study partici pants. In men and women, carriers of the -514T allele had higher HDL-C and apolipoprotein A-I (apoAI) concentrations compared with noncarriers. The hi gher HDL-C levels associated with the -514T allele was due to an increase i n the HDL2-C subfraction, and this association was stronger in women compar ed with men (P=0.0043 versus 0.0517). To gain further understanding about t he metabolic basis of these effects, HDL and low density lipoprotein (LDL) subclass profiles were measured by using automated nuclear magnetic resonan ce spectroscopy and gradient gel electrophoresis, respectively. The associa tion of the -514T allele with higher HDL-C levels seen in men and women was primarily due to significant increases in the large HDL subfractions (size range 8.8 to 13.0 nm). In contrast, there was no relationship between the hepatic lipase polymorphism at position -514 and the LDL particle size dist ribution after adjustment for familial relationships, age, body mass index, smoking, alcohol intake, use of beta-blockers, apoE genotype, and menopaus al status and estrogen therapy in women. Moreover, multiple regression anal yses suggested that the C-514T polymorphism contributed significantly to th e variability of HDL particle size in men and women (P<0.04). Thus, our res ults show that the C-514T polymorphism in the hepatic lipase gene is associ ated with significant variations in the lipoprotein profile in men and wome n.