Hepatic lipase gene-514C/T polymorphism and premature coronary heart disease

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 CHID patients aged under 50 years and in 642 Caucasian community recruited subjects without historical evidence of CHID. 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% Cl: 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 CHID 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 CHID 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% Cl 0.09 - 0.126). It can lead to mistyping of C as T alleles in C/T heterozygotes, resulting in overestimation of -514T 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 CHID in males is attributable to impairment of TG rich lipoprotein metabolism and reverse cholesterol transport. (C) 2002 Lippincott Williams Wilkins.