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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2701.)
© 1999 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

From the Department of Medicine, Divisions of Metabolism, Endocrinology, and Nutrition (M.C.C., J.E.H., J.Q.P., J.D.B.) and Medical Genetics (S.S.D.); and the Department of Family and Child Nursing (E.S.M.), University of Washington, Seattle.

Correspondence to Dr Molly C. Carr, Division of Metabolism, Endocrinology, and Nutrition, Box 356426, University of Washington, Seattle, WA 98195-6426. E-mail carr{at}u.washington.edu

Abstract—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 (GA^-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.

Key Words: cholesterol • lipoprotein • visceral obesity • LIPC • triglyceride

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				References Circulation, December 17, 2002; 106(25): 3373 - 3421. [Full Text]

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				J. E. Hokanson, S. Cheng, J. K. Snell-Bergeon, B. A. Fijal, M. A. Grow, C. Hung, H. A. Erlich, J. Ehrlich, R. H. Eckel, and M. Rewers A Common Promoter Polymorphism in the Hepatic Lipase Gene (LIPC-480C>T) Is Associated With an Increase in Coronary Calcification in Type 1 Diabetes Diabetes, April 1, 2002; 51(4): 1208 - 1213. [Abstract] [Full Text] [PDF]

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				M. C. Carr, J. E. Hokanson, A. Zambon, S. S. Deeb, P. H. R. Barrett, J. Q. Purnell, and J. D. Brunzell The Contribution of Intraabdominal Fat to Gender Differences in Hepatic Lipase Activity and Low/High Density Lipoprotein Heterogeneity J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2831 - 2837. [Abstract] [Full Text] [PDF]

				S. J. Murdoch, M. C. Carr, J. E. Hokanson, J. D. Brunzell, and J. J. Albers PLTP activity in premenopausal women: relationship with lipoprotein lipase, HDL, LDL, body fat, and insulin resistance J. Lipid Res., February 1, 2000; 41(2): 237 - 244. [Abstract] [Full Text]

				S. S. Deeb and R. Peng The C-514T polymorphism in the human hepatic lipase gene promoter diminishes its activity J. Lipid Res., January 1, 2000; 41(1): 155 - 158. [Abstract] [Full Text]

				M.C. Carr, A.F. Ayyobi, S.J. Murdoch, S.S. Deeb, and J.D. Brunzell Contribution of Hepatic Lipase, Lipoprotein Lipase, and Cholesteryl Ester Transfer Protein to LDL and HDL Heterogeneity in Healthy Women Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 667 - 673. [Abstract] [Full Text] [PDF]