Objective: To assess the association of S447X mutation and Hind III polymorphism in the lipoprotein lipase gene with dyslipidemia of the metabolic syndrome in patients with essential hypertension.
Methods: A total of 983 patients were randomly selected from those with hypertension (diagnosed in the Community-based Comprehensive Studies on Prevention and Control of Hypertension Project in China) and those not treated with anti-hypertensive medications for at least in 2 weeks immediately before blood collection. Among them were 389 subjects with dyslipidemia and 594 subjects without dyslipidemia. The definition of dyslipidemia in patients with hypertension was used only when triglyceride or HDL-cholesterol was at abnormal level. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine Ser447stop mutation and Hind III polymorphism in LPL gene.
Results: Linkage disequilibrium between the two sites was observed, with three major haplotypes identified: H+S, H-S, and H-X. The LPL gene S447X mutation and H-X haplotype were significantly associated with dyslipidemia (OR=0.547, 95%CI: 0.348-0.859 for S447X mutation; OR=0.537, 95%CI: 0.328-0.880 for H-X haplotype) in male, both by themselves and after adjustment for age, body mass index, smoking, alcohol intake, systolic blood pressure, diastolic blood pressure, education and serum glucose. The LPL H- carriers and H-S haplotype were significantly associated with dyslipidemia (OR=0.575, 95%CI: 0.358-0.923) in female after multivariate adjustment. Moreover, compared with the H+S haplotype, the H-X haplotypes were associated with significantly lower TG and Log (TG/HDL-C) levels in both men and women, and with higher HDL-C levels in women; whereas no significant difference was observed between the H-S and H+S haplotype. Compared with the H-S haplotype, the H-X haplotypes had significant effect on the HDL-C levels in women.
Conclusion: The LPL H-X haplotype was one of the protective factors of dyslipidemia of metabolic syndrome in hypertensive patients. It is significantly associated with low triglyceride, log triglyceride-to-HDL-cholesterol ratio and high HDL-cholesterol levels. S447X mutation does not explain all the effect associated with the Hind III polymorphism, although the effect on serum lipids associated with the H-X haplotype appeared to be mainly mediated by the S447X mutation. It is possible that some functional mutations in the LPL gene besides the S447X mutation are in linkage disequilibrium with the Hind III polymorphism.