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 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 x mL(-1) x 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 x mL(-1) x 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.
Carr
M C
MC
Department of Medicine, Divisions of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle 98195-6426, USA. carr@u.washington.edu
Hokanson
J E
JE
Deeb
S S
SS
Purnell
J Q
JQ
Mitchell
E S
ES
Brunzell
J D
JD
D000005:Abdomen; D000273:Adipose Tissue / Q000201:enzymology*; D000328:Adult; D008076:Cholesterol, HDL / Q000097:blood; D004789:Enzyme Activation / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000201:enzymology; D011110:Polymorphism, Genetic; D017697:Premenopause; D011401:Promoter Regions, Genetic / Q000502:physiology*; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D014280:Triglycerides; D008049:Lipase