Relationship between a Novel Polymorphism of Hepatic Lipase Gene and Coronary Artery Disease

( 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.