Relationship between a novel polymorphism of hepatic lipase gene and coronary artery disease

Hepatic lipase (HL) is a lipolytic enzyme involved in the catabolism of plasma lipoproteins, and is an important determinant of high density lipoproteins ( 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 concentration have been investigated thoroughly, but to date, little is known about this in Chinese. In present study, the SNPs of the HL gene were analyzed. The promoter region and all the 9 exons with their flanking sequences of the HL gene were amplified 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%, chi(2) = 4.181, df = 2, P = 0.041). The prevalence of the - 2C allele was significantly higher in the CAD patients than in control subjects (chi(2) = 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 patients had a significantly higher HDL-cholesterol level than the noncarriers [(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 the variation of HDL-cholesterol concentration and therefore affect the risk of CAD in Chinese.