Hepatic lipase C-480T polymorphism modifies the effect of HDL cholesterol on the risk of acute myocardial infarction in men: a prospective population based study.

P revious studies have revealed an inverse association between high density lipoprotein cholesterol (HDL-C) levels and the risk of acute myocardial infarction (AMI). 2 HDL-C level is modulated by genetic factors as well as environmental factors such as obesity, smoking, and physical exercise. Hepatic lipase (HL) is a lipolytic enzyme in lipoprotein metabolism, functioning as a phospholipase, an acylglycerol hydrolase, and a ligand of cell surface glycosaminoglycans, hydrolysing triglyceride-rich lipoprotein particles. Recently, it has been reported that HL is synthesised by macrophages. The HL gene variation has a significant effect on the variability of HDL-C in the population. 6 The functional HL promoter C-480T transition, also referred to as (-514C/T), leads to three common genotypes: CC, CT, and TT. The C and T alleles are associated with high and low HL activity, respectively. However, the common polymorphisms of HL (-480T), cholesterol ester transfer protein (CETP) (TaqIB), lipoprotein lipase (S447X), and lecithin cholesterol acyl transferase (S208T) contribute only about 2.5% to the variance of HDL-C in the population. This suggests that the HL C-480T polymorphism and HDL-C levels are different factors, and studying their interaction is justified. One previous study has shown that there might be an interaction between CETP gene polymorphism and HDL-C on the risk of myocardial infarction. This result raises the possibility that other polymorphisms associated with HDL-C—for example, HL gene polymorphism—might interact with HDL-C and thus modify the risk of AMI. In fact, an effect of the C-480T polymorphism on coronary artery disease (CAD) has been sought in several studies with both negative 12 and positive findings. One possible reason for the mixed results may be the interaction between HL C-480T genotype and HDL levels on CAD, a hypothesis not studied previously. To address this question, and to prospectively examine the relationship between the C-480T polymorphism of the HL gene and subsequent occurrence of AMI, we conducted a population based study in a cohort of Finnish men of middle age and with no previous history of coronary disease. We also explored the interaction between C-480T polymorphism and HDL-C levels on the risk of developing AMI.