A hepatic lipase gene promoter polymorphism attenuates the increase in hepatic lipase activity with increasing intra-abdominal fat in women

High hepatic lipase (HL) activity is associated with an atherogenic lipoprotein profile of small, dense LDL particles and lower HDL2-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 HDL2-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 HDL2-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.