Hepatic lipase gene variation is related to coronary reactivity in healthyyoung men

Background Impaired coronary flow reserve (CFR) can be used to indicate vas cular dysfunction before the appearance of angiographic lesions. The hepati c lipase (HL) gene has a functional promoter polymorphism at position C-480 T, which affects transcription and leads to high activity (C/C) and low act ivity (C/T, T/T) genotypes. These genotypes modulate HL activity, but their role in coronary artery disease is controversial and the effect on coronar y function has not been studied. We investigated whether HL genotypes are a ssociated with coronary artery function in healthy young men. Materials and methods We studied 49 healthy, mildly hypercholesterolemic me n (aged 35 +/- 4 years). Myocardial blood now was measured at rest and duri ng adenosine induced hyperaemia with positron emission tomography using [O- 15] H2O. HL genotype was determined by PCR and Nla III enzyme digestion. Results Resting myocardial blood flow was not statistically different in su bjects with high and low activity HL genotypes. However, CFR (the ratio of adenosine now to resting flow) was 24% higher (4.62 +/- 1.52 vs. 3.73 +/- 1 .08 mL g(-1) min(-1), P = 0.024) in men with the high activity genotype (n = 26) than in those with low activity (n = 23). In multivariate analysis, t he HL genotype remained a significant predictor of CFR (P = 0.038) after ad justing for age, body mass index, serum lipids and smoking. Conclusions The findings of our preliminary study suggest that the C-480T p olymorphism of the HL gene may modify coronary reactivity and reflect diffe rences in the early pathogenesis of coronary dysfunction in these healthy y oung men. If the association between HL polymorphism and impaired CFR is al so present in subjects with other dyslipoproteinemias, the HL polymorphism could be a new risk factor for cardiovascular disease.