Related Experiment Videos
Hepatic lipase gene -514 C/T polymorphism and premature coronary heart disease
Juying Ji1, Carly E Herbison, Cyril D S Mamotte
1Cardiovascular Genetics Laboratory, Royal Perth Hospital, Department of Medicine, University of Western Australia and the Western Australian Heart Research Institute, Australia.
Insights
The hepatic lipase -514 C/T gene variant is linked to altered plasma lipids and a higher risk of coronary heart disease (CHD) in males, potentially due to impaired lipoprotein metabolism.
Area of Science:
- Genetics
- Cardiovascular Disease Research
- Lipid Metabolism
Background:
- A common polymorphism in the hepatic lipase (HL) gene promoter, -514C/T, influences enzyme activity and plasma lipoprotein levels.
- The association between this HL gene polymorphism and coronary heart disease (CHD) requires further investigation.
Purpose of the Study:
- To investigate the relationship between the HL -514 C/T polymorphism and CHD in Caucasian subjects.
- To examine the impact of the HL -514 C/T polymorphism on plasma lipid profiles in relation to CHD status.
Main Methods:
- A case-control study involving 562 Caucasian CHD patients under 50 and 642 healthy Caucasian controls.
- Genotyping for the HL -514 C/T polymorphism and analysis of plasma lipid levels (HDL-cholesterol, triglycerides, total cholesterol, LDL-cholesterol).
Main Results:
- Male CHD patients exhibited a higher carrier rate for the -514 T allele (41%) compared to controls (33%), indicating a predisposition to CHD.
- In male CHD patients, the T allele was associated with higher HDL-cholesterol and more frequent occurrence in those with high triglycerides.
- A novel polymorphism (-592A/G) was identified, potentially leading to misclassification of -514 C/T genotypes.
Conclusions:
- The T allele of the hepatic lipase -514 C/T polymorphism is associated with altered plasma lipid profiles.
- The increased CHD risk in males with the -514 T allele may stem from impaired triglyceride-rich lipoprotein metabolism and reverse cholesterol transport.
Background:
A common polymorphism in the hepatic lipase (HL) gene promoter, -514C/T, affecting enzyme activity, has been associated with alterations in plasma lipoprotein levels. However a relationship with coronary heart disease (CHD) is less well documented.
Design And Methods:
We studied HL -514 C/T in 562 Caucasian CHD patients aged under 50 years and in 642 Caucasian community recruited subjects without historical evidence of CHD.
Results:
Male CHD subjects (n = 490) had a 41% carrier rate for the C to T substitution, compared with 33% in corresponding controls (n = 330), [OR = 1.42 (95% CI:1.06-1.90), P < 0.02], T allele frequencies being 0.231 and 0.177 respectively [OR = 1.39 (1.08-1.78), P < 0.01]. In male CHD subjects, the T allele was associated with higher HDL-cholesterol (HDL-C) (CC: 0.95 +/- 0.24 (SD); CT: 1.04 +/- 0.41; TT: 1.01 +/- 0.20 mmol/l, P = 0.02, ANOVA) but the trend was not significant in females. In male CHD patients the T allele was more frequently encountered in those with high (> 4.5 mmol/l) than in those with low triglycerides [68% vs. 39%, OR = 3.13 (1.54-6.67), P = 0.001]. In community control subjects, the T allele was associated with a trend to higher HDL-C levels, the significance varying between subgroups while, in males, serum total and LDL-cholesterol were significantly lower in T homozygotes than in the other two genotypes (LDL-C: 2.73 +/- 0.63 vs. 3.56 +/- 0.95 mmol/l; P = 0.01). During the course of this study, a previously unreported promoter region polymorphism was found exclusively on -514C chromosomes (-592A/G, A allele frequency 0.108, 95% CI 0.09 - 0.126). It can lead to mistyping of C as T alleles in C/T heterozygotes, resulting in overestimation of -514 T homozygotes.
Conclusions:
The T allele of the hepatic lipase -514 C/T polymorphism is associated with changes in plasma lipids. The superficially paradoxical predisposition to CHD in males is attributable to impairment of TG rich lipoprotein metabolism and reverse cholesterol transport.