A Hepatic Lipase Gene Promoter Polymorphism Attenuates the Increase in Hepatic Lipase Activity With Increasing Intra-abdominal Fat in Women

Abstract

Abstract —High hepatic lipase (HL) activity is associated with an atherogenic lipoprotein profile of small, dense LDL particles and lower HDL 2 -C. Intra-abdominal fat (IAF) is positively associated with HL activity. A hepatic lipase gene ( LIPC ) promoter variant (G→A −250 ) is associated with lower HL activity, higher HDL 2 -C, and less dense LDL particles. To determine whether the LIPC promoter polymorphism acts independently of IAF to regulate HL, 57 healthy, premenopausal women were studied. The LIPC promoter A allele was associated with significantly lower HL activity (GA/AA=104±34 versus GG=145±57 nmoles · mL −1 · min −1 , P =0.009). IAF was positively correlated with HL activity ( r =0.431, P <0.001). Multivariate analysis revealed a strong relationship between both the LIPC promoter genotype ( P =0.001) and IAF ( P <0.001) with HL activity. The relationship between IAF and HL activity for carriers and noncarriers of the A allele was curvilinear with the carriers having a lower apparent maximum level of plasma HL activity compared with noncarriers (138 versus 218 nmoles · mL −1 · min −1 , P <0.001). In addition, the LIPC A allele was associated with a significantly higher HDL 2 -C (GA/AA=16±7 versus GG=11±5 mg/dL, P =0.003). We conclude that the LIPC promoter A allele attenuates the increase in HL activity due to IAF in premenopausal women.