Hepatic lipase polymorphism and increased risk of peripheral arterial disease.

Abstract

BACKGROUND: Hepatic lipase plays a key role in the metabolism of pro-atherogenic and anti-atherogenic lipoproteins affecting their plasma level as well as their physico-chemical properties. We hypothesized single nucleotide polymorphisms in the promoter region of the hepatic lipase gene to be associated with an increased risk for peripheral arterial disease (PAD). METHODS: A total of 241 patients with PAD and 241 controls matched for sex and age (+/-2 years) were genotyped cross-sectionally for the --250 single nucleotide polymorphism in the hepatic lipase promoter. RESULTS. The frequency for the -250 A allele in patients with PAD was 0.203, whereas it was 0.147 in the controls (P=0.022). Hepatic lipase promoter polymorphism distribution remained significantly different between cases and controls after multivariate logistic regression analysis (P=0.021). The odds ratio of the -250 A hepatic lipase allele for the PAD was 1.69 (95% confidence interval of 1.08-2.64), when adjusted for current smoking, arterial hypertension, cholesterol, triglycerides, HbA(1C), total homocysteine and high sensitivity C-reactive protein. CONCLUSION: Previous data in patients with ischaemic heart disease have suggested a pro-atherogenic role of low hepatic lipase levels. Our results extend these data to the vascular territory of the lower limbs, such that hepatic lipase promoter variation represents a genetic risk factor of PAD.