( Department of Medical Genetics, West China Hospital, Sichuan University, Chengdu 610041, China;
¹Institute of Forensic Medicine, West China Medical Center, Sichuan University, Chengdu 610041, China;
²Department of Cardiology, West China Hospital, Sich uan University, Chengdu 610041, China )

Abstract

Hepatic lipase (HL) is a lipolytic enzyme involved in the catabolism of plasma lipoproteins, and is an important determinant of high density lipoprote ins(HDL) concentration and low density lipoproteins(LDL) subclass distribution. Accordingly, HL activity may influence body's susceptibility to coronary artery disease (CAD). Association on the single nucleotide polymorphisms (SNPs) in the HL gene to post-heparin plasma HL activity and the plasma HDL-cholesterol concent ration have been investigated thoroughly, but to date, little is known about th is in Ch i nese. In present study, the SNPs of the HL gene were analyzed. The promoter regi on and all the 9 exons with their flanking sequences of the HL gene were amp lifi ed from the Chinese patients with CAD and normal controls by PCR technique, and the PCR products were detected by denaturing high performance liquid chromatography (DHPLC) and sequenced with a dideoxy terminal termination method. As the result, a novel SNP-2T↷C in the promoter of HL gene was found. Compared with the control group, more CAD patients carried the -2C allele(TC+CC) (57.9% versus 42.7%, χ² =4.181, df=2, P=0.041). The prevalence of the -2C all ele was signifi cantly higher in the CAD patients than in control subjects (χ²=3.988, df=1, P=0.046) and the odds ratio(OR) of -2C allele associated with the risk of CAD is 1.58 [95% confidence interval(CI): 1.01--2.47]. The -2C allele homozygous carriers in the CAD pat ients had a significantly higher HDL-cholesterol level than the noncar riers [(1.13±0.24) mmol/L versus (0.91±0.14) mmol/L, P<0.05]. These suggest that a T->C substitution at -2 of the HL promoter may be associated with th evariation of HDL-cholesterol concentration and therefore affect the risk of CAD in Chinese.