This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carr, M. C. Articles by Brunzell, J. D. Search for Related Content PubMed PubMed Citation Articles by Carr, M. C. Articles by Brunzell, J. D. Related Collections Lipid and lipoprotein metabolism Risk Factors Gene expression

(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

This article has been cited by other articles:

				S. Imamura, J. Kobayashi, K. Nakajima, S. Sakasegawa, A. Nohara, T. Noguchi, M. A. Kawashiri, A. Inazu, S. S. Deeb, H. Mabuchi, et al. A novel method for measuring human lipoprotein lipase and hepatic lipase activities in postheparin plasma J. Lipid Res., July 1, 2008; 49(7): 1431 - 1437. [Abstract] [Full Text] [PDF]

				D. Greco, A. Kotronen, J. Westerbacka, O. Puig, P. Arkkila, T. Kiviluoto, S. Laitinen, M. Kolak, R. M. Fisher, A. Hamsten, et al. Gene expression in human NAFLD Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1281 - G1287. [Abstract] [Full Text] [PDF]

				E. Nisoli, E. Clementi, M. O. Carruba, and S. Moncada Defective Mitochondrial Biogenesis: A Hallmark of the High Cardiovascular Risk in the Metabolic Syndrome? Circ. Res., March 30, 2007; 100(6): 795 - 806. [Abstract] [Full Text] [PDF]

				Y.-M. Fan, P. Dastidar, H. Jokela, R. Punnonen, and T. Lehtimaki Hepatic Lipase C-480T Genotype-Dependent Benefit from Long-Term Hormone Replacement Therapy for Atherosclerosis Progression in Postmenopausal Women J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3786 - 3792. [Abstract] [Full Text] [PDF]

				N. Yi, S. Chiu, D. B. Allison, J. S. Fisler, and C. H. Warden Epistatic interaction between two nonstructural loci on chromosomes 7 and 3 influences hepatic lipase activity in BSB mice J. Lipid Res., November 1, 2004; 45(11): 2063 - 2070. [Abstract] [Full Text] [PDF]

				D. B. Carr, K. M. Utzschneider, R. L. Hull, K. Kodama, B. M. Retzlaff, J. D. Brunzell, J. B. Shofer, B. E. Fish, R. H. Knopp, and S. E. Kahn Intra-Abdominal Fat Is a Major Determinant of the National Cholesterol Education Program Adult Treatment Panel III Criteria for the Metabolic Syndrome Diabetes, August 1, 2004; 53(8): 2087 - 2094. [Abstract] [Full Text] [PDF]

				B. Todorova, A. Kubaszek, J. Pihlajamaki, J. Lindstrom, J. Eriksson, T. T. Valle, H. Hamalainen, P. Ilanne-Parikka, S. Keinanen-Kiukaanniemi, J. Tuomilehto, et al. The G-250A Promoter Polymorphism of the Hepatic Lipase Gene Predicts the Conversion from Impaired Glucose Tolerance to Type 2 Diabetes Mellitus: The Finnish Diabetes Prevention Study J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2019 - 2023. [Abstract] [Full Text] [PDF]

				M. C. Carr, J. D. Brunzell, and S. S. Deeb Ethnic differences in hepatic lipase and HDL in Japanese, black, and white Americans: role of central obesity and LIPC polymorphisms J. Lipid Res., March 1, 2004; 45(3): 466 - 473. [Abstract] [Full Text] [PDF]

				J. E. Hokanson, M. I. Kamboh, S. Scarboro, R. H. Eckel, and R. F. Hamman Effects of the Hepatic Lipase Gene and Physical Activity on Coronary Heart Disease Risk Am. J. Epidemiol., November 1, 2003; 158(9): 836 - 843. [Abstract] [Full Text] [PDF]

				E S. Tai, D. Corella, M. Deurenberg-Yap, J. Cutter, S. K. Chew, C. E. Tan, and J. M. Ordovas Dietary Fat Interacts with the -514C>T Polymorphism in the Hepatic Lipase Gene Promoter on Plasma Lipid Profiles in a Multiethnic Asian Population: The 1998 Singapore National Health Survey J. Nutr., November 1, 2003; 133(11): 3399 - 3408. [Abstract] [Full Text] [PDF]

				S. S. Deeb, A. Zambon, M. C. Carr, A. F. Ayyobi, and J. D. Brunzell Hepatic lipase and dyslipidemia: interactions among genetic variants, obesity, gender, and diet J. Lipid Res., July 1, 2003; 44(7): 1279 - 1286. [Abstract] [Full Text] [PDF]

				R. V. Andersen, H. H. Wittrup, A. Tybjaerg-Hansen, R. Steffensen, P. Schnohr, and B.o. G. Nordestgaard Hepatic lipase mutations,elevated high-density lipoprotein cholesterol, and increased risk of ischemic heart disease: The Copenhagen City Heart Study J. Am. Coll. Cardiol., June 4, 2003; 41(11): 1972 - 1982. [Abstract] [Full Text] [PDF]

				K. L. Herbst, J. K. Amory, J. D. Brunzell, H. A. Chansky, and W. J. Bremner Testosterone administration to men increases hepatic lipase activity and decreases HDL and LDL size in 3 wk Am J Physiol Endocrinol Metab, June 1, 2003; 284(6): E1112 - E1118. [Abstract] [Full Text] [PDF]

				D. J. Nieves, M. Cnop, B. Retzlaff, C. E. Walden, J. D. Brunzell, R. H. Knopp, and S. E. Kahn The Atherogenic Lipoprotein Profile Associated With Obesity and Insulin Resistance Is Largely Attributable to Intra-Abdominal Fat Diabetes, January 1, 2003; 52(1): 172 - 179. [Abstract] [Full Text] [PDF]

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

				S. J. Murdoch, M. C. Carr, H. Kennedy, J. D. Brunzell, and J. J. Albers Selective and independent associations of phospholipid transfer protein and hepatic lipase with the LDL subfraction distribution J. Lipid Res., August 1, 2002; 43(8): 1256 - 1263. [Abstract] [Full Text] [PDF]

				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]

				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]

				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]