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 (G3 A Ϫ250 ) 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

more »

... promoter A allele was associated with significantly lower HL activity (GA/AAϭ104Ϯ34 versus GGϭ145Ϯ57 nmoles ⅐ mL Ϫ1 ⅐ min Ϫ1 , Pϭ0.009). IAF was positively correlated with HL activity (rϭ0.431, PϽ0.001). Multivariate analysis revealed a strong relationship between both the LIPC promoter genotype (Pϭ0.001) and IAF (PϽ0.001) 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 ⅐ mL Ϫ1 ⅐ min Ϫ1 , PϽ0.001). In addition, the LIPC A allele was associated with a significantly higher HDL 2 -C (GA/AAϭ16Ϯ7 versus GGϭ11Ϯ5 mg/dL, Pϭ0.003). We conclude that the LIPC promoter A allele attenuates the increase in HL activity due to IAF in premenopausal women.