Influence of the angiotensin-converting enzyme gene insertion/deletion polymorphism on lipoprotein/lipid response to gemfibrozil

Evidence suggests that fibrate therapy reduces the risk of recurrent coronary heart disease among men with low levels of high density lipoprotein cholesterol (HDL-C). Indirect observations and new possible biological pathways suggest that the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism might modulate the lipoprotein/lipid profile and its response to fibrate therapy. To assess the possible interaction between fibrate therapy and such variants on plasma lipid and lipoprotein levels, 65 dyslipidemic abdominally obese men were treated for 6 months with or without gemfibrozil (600 mg twice daily). No differences in baseline plasma lipid and lipoprotein levels were found between genotype groups except for the HDL(3)-C subfraction, which was higher in the DD group (p = 0.02). A two-way factorial ANOVA was used to evaluate the effect of the genotype (DD homozygotes vs I allele carriers), the treatment (placebo vs gemfibrozil), and the interaction between these two independent variables on changes observed in lipid and lipoprotein concentrations. A significant genotype-by-treatment interaction (p = 0.02) was found for the plasma HDL-C response to the intervention program. In fact, having the DD genotype and being treated with gemfibrozil had a synergical effect on HDL-C levels. The results of this study suggest that the ACE I/D polymorphism influences the effect of gemfibrozil on plasma HDL-C levels.