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

Molly C. Carr, John E. Hokanson, Samir S. Deeb, Jonathan Q. Purnell, Ellen S. Mitchell, John D. Brunzell
1999 Arteriosclerosis, Thrombosis and Vascular Biology  
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.
doi:10.1161/01.atv.19.11.2701 pmid:10559014 fatcat:otgf7awl5zf3bjp5ag2rri6qcy