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Journal of Lipid Research, Vol. 43, 1595-1601, October 2002
Copyright © 2002 by Lipid Research, Inc.

A novel allele in the promoter of the hepatic lipase is associated with increased concentration of HDL-C and decreased promoter activity

Zhiguang Su^*,, Sizhong Zhang^1,*,, Daniel W. Nebert, Li Zhang^**, Dejia Huang^**, Yiping Hou, Linchuan Liao and Cuiying Xiao^*,

^* Department of Medical Genetics, West China Hospital, Sichuan University, China
Key Laboratory of Biotherapy of Human Disease, Ministry of Education, P.R. China
Department of Environmental Health, Department of Pediatrics & Developmental Biology/Division of Human Genetics, University of Cincinnati Medical Center, Cincinnati, OH
^** Department of Cardiology, West China Hospital, Sichuan University, China

¹ To whom correspondence should be addressed. e-mail: szzhang{at}mcwcums.com

Hepatic lipase (HL) is a lipolytic enzyme involved in the metabolism of plasma lipoproteins, especially HDLs. Association of the polymorphisms in the promoter region of the LIPC gene to post-heparin plasma HL activity and the plasma HDL-C concentration has been investigated thoroughly, but to date little is known about this in the Chinese. In the present study, we analyzed the polymorphisms in the promoter region of LIPC gene in Chinese patients with coronary artery disease (CAD) using denaturing high performance liquid chromatography (DHPLC) and DNA sequencing. As the result, a novel single nucleotide polymorphism -586T-to-C was identified and no linkage of this variant with other polymorphisms in the promoter was found. Compared with the nonsymptomatic control subjects, excess of carriers of the -586T/C substitution were detected in the CAD patients (43% vs. 31%, ² = 4.597, degree of freedom = 2, P = 0.032).The –586C allele carriers in the CAD patients had a significantly higher HDL-C level than the noncarriers (1.13 ± 0.24 mmol/l vs. 0.91 ± 0.14 mmol/l, P < 0.05). To test the functionality of this substitution, luciferase-reporter assays was performed in HepG2 cells. Promoter activity of the -586C construct was decreased 2-fold than the -586T construct.

Our studies suggest that a T-to-C substitution at -586 of the LIPC promoter is associated with a lowered HL activity and that this variation may contribute to the increased plasma HDL-C concentration in the Chinese.

Abbreviations: CAD, coronary artery disease; DHPLC, denaturing high performance liquid chromatography; HL, hepatic lipase; HDL-C, high density lipoprotein cholesterol; SNP, single nucleotide polymorphism

Supplementary key words LIPC promoter • single nucleotide polymorphism • coronary artery disease • transient transfection • single nucleotide polymorphism

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