Original Article

Hepatic lipase activity influences high density lipoprotein subclass distribution in normotriglyceridemic men: genetic and pharmacological evidence

Correspondence to: Jonathan C. Cohen

Several studies have reported an inverse relationship between hepatic lipase activity and plasma high density lipoprotein (HDL) cholesterol concentrations. The purpose of the present study was to determine whether genetic and pharmacological variation in hepatic lipase activity alters the distribution of HDL subclasses. Two independent analytical methods (nuclear magnetic resonance and gradient gel electrophoresis) were used to compare HDL subclass distributions in 11 homozygotes for the -514C allele of hepatic lipase and in 6 homozygotes for the -514T allele. Mean hepatic lipase activity was 45 ± 15 mmol · l^-1 · hr^-1 in -514C homozygotes and 20 ± 7 mmol · l^-1 · hr^-1 in -514T homozygotes. Both analytical methods indicated that HDL_2b was significantly higher and HDL_3a was significantly lower in -514T homozygotes than in -514C homozygotes. No differences were noted in the other HDL fractions (HDL_2a, HDL_3b, and HDL_3c). To determine the effects of increased hepatic lipase activity, 20 men were given the synthetic anabolic steroid, stanozolol. Stanozolol treatment increased hepatic lipase activity more than two-fold (38 ± 18 to 85 ± 25 mmol · l^-1 · hr^-1), and markedly reduced the plasma concentrations of the larger HDL subclasses (HDL_2b and HDL_2a). The plasma concentrations of the smallest HDL subclasses (HDL_3b and HDL_3c) were unchanged by stanozolol treatment.

Taken together, these genetic and pharmacological data indicate that variation in hepatic lipase activity has highly specific effects on the distribution of HDL subclasses in the circulation.—Grundy, S. M., G. L. Vega, J. D. Otvos, D. L. Rainwater, and J. C. Cohen. Hepatic lipase activity influences high density lipoprotein subclass distribution in normotriglyceridemic men: genetic and pharmacological evidence. J. Lipid Res. 1999. 40: 229–234.

Supplementary key words: polymorphism, hepatic lipase, high density lipoprotein, nuclear magnetic resonance, particle size

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