Hepatic lipase mutation may reduce vascular disease prevalence in hemodialysis patients with high CETP levels

Abstract

Uremic dyslipidemia characterized by reduced high-density lipoprotein (HDL) cholesterol levels is one of the major contributors to the high incidence of cardiovascular disease in hemodialysis patients. Hepatic lipase (HL), together with cholesteryl ester transfer protein (CETP), may not only promote reverse cholesterol transport but also enhance production of small, dense, more atherogenic low-density lipoprotein (LDL). A common C-514T mutation of the promoter region of the HL gene reportedly increases HDL cholesterol levels. However, whether the HL mutation is antiatherogenic or proatherogenic has remained unknown in uremic patients and the general population. We investigated the influence of the mutation and its interaction with CETP on HDL cholesterol levels and the apparent atherosclerotic complications in 183 hemodialysis patients aged over 30 years who had received no antilipemic drugs. In patients with CETP levels > or =2.2 microg/mL [high CETP (HCT) group, N = 97], subjects with the TT genotype had a significantly higher level of HDL cholesterol than those without TT genotype (56.8 +/- 15.9 mg/dL vs. 45.7 +/- 13.4 mg/dL, P < 0.001), but not in patients with CETP levels <2.2 microg/mL [low CETP (LCT) group]. Multiple linear regression analysis showed that the TT genotype was a major independent positive determinant for HDL cholesterol levels in the HCT not LCT group. Among the HCT group patients, subjects with the TT genotype (N = 25) had a tendency toward lower prevalence of vascular disease than those without TT genotype (N = 72) (4.0% vs. 22.2%, P < 0.07). In this subgroup, TT genotype had an independent odds ratio of 0.041 (95% CI 0.002 to 0.75, P < 0.05) after adjusting for other risk factors. The TT genotype of HL mutation may serve as a protective factor against vascular disease by increasing HDL cholesterol levels in hemodialysis patients with higher CETP levels.