Clin Genet 2002: 62: 45–52 Copyright C Blackwell Munksgaard 2002 Printed in Denmark. All rights reserved CLINICAL GENETICS 0009-9163 Original Article Influence of the angiotensin-converting enzyme gene insertion/deletion polymorphism on lipoprotein/lipid response to gemfibrozil Bosse ´ Y, Vohl M-C, Dumont M, Brochu M, Bergeron J, Despre ´s J-P, Y Bosse ´ a , M-C Vohl b,c , Prud’homme D. Influence of the angiotensin-converting enzyme gene M Dumont a , M Brochu d , insertion/deletion polymorphism on lipoprotein/lipid response to J Bergeron b , J-P Despre ´s b,c,e gemfibrozil. and D Prud’homme f Clin Genet 2002: 62: 45–52. C Blackwell Munksgaard, 2002 a Physical Activity Sciences Laboratory, Kinesiology Division, Department of Social Evidence suggests that fibrate therapy reduces the risk of recurrent and Preventive Medicine, b Lipid Research coronary heart disease among men with low levels of high density Center, CHUL Research Center, c Food lipoprotein cholesterol (HDL-C). Indirect observations and new possible Sciences and Nutrition Department, Laval biological pathways suggest that the angiotensin-converting enzyme University, Que ´bec, Canada; d Department (ACE) insertion/deletion (I/D) polymorphism might modulate the of Kinesiology, University of Montreal, e The lipoprotein/lipid profile and its response to fibrate therapy. To assess the Quebec Heart Institute, Que ´bec, Canada; f Human Kinetics, Faculty of Health possible interaction between fibrate therapy and such variants on plasma Sciences, University of Ottawa, Ontario, lipid and lipoprotein levels, 65 dyslipidemic abdominally obese men were Canada treated for 6months with or without gemfibrozil (600mg twice daily). No differences in baseline plasma lipid and lipoprotein levels were found Key words: ACE I/D polymorphism – between genotype groups except for the HDL 3 -C subfraction, which was gemfibrozil – HDL-cholesterol – visceral higher in the DD group (p Ω0.02). A two-way factorial ANOVA was used obesity to evaluate the effect of the genotype (DD homozygotes vs I allele Corresponding author: Denis Prud’homme, carriers), the treatment (placebo vs gemfibrozil), and the interaction MD, MSc, Director, School of Human between these two independent variables on changes observed in lipid and Kinetics, Faculty of Health Sciences, lipoprotein concentrations. A significant genotype-by-treatment interaction University of Ottawa, 125 University St., (p Ω0.02) was found for the plasma HDL-C response to the intervention PO Box 450, Station A, Ottawa, Ontario, program. In fact, having the DD genotype and being treated with Canada K1N 6N5. Tel.: 613 562 5851; fax: gemfibrozil had a synergical effect on HDL-C levels. The results of this 613 562 5149; e-mail: denisp/uottawa.ca study suggest that the ACE I/D polymorphism influences the effect of Received 22 January 2002, revised and gemfibrozil on plasma HDL-C levels. accepted for publication 14 March 2002 Gemfibrozil, a fibric acid derivative, is an effective lipid-modifying agent with clinical benefits in both primary and secondary prevention trials (1, 2). De- spite its marginal impact on plasma low density lipoprotein cholesterol (LDL-C) levels, it signifi- cantly increases plasma high density lipoprotein cholesterol (HDL-C) concentrations while sub- stantially decreasing plasma triglyceride levels. Al- though fibrate is the preferred class of drugs to increase HDL-C levels among patients with low HDL-C concentration, there is documented indi- vidual variation in plasma HDL-C response to dif- ferent treatment intervention, including endurance exercise training (3), dietary intervention (4) and 45 drug therapy (5), which seems to be influenced by genetic factors. For instance, a previous investiga- tion has demonstrated that the individual response to gemfibrozil could be partly explained by poly- morphisms in genes coding for apolipoproteinB (apoB) and apoA1/CIII (6). An interaction between the angiotensin-convert- ing enzyme (ACE) insertion/deletion (I/D) poly- morphism and the plasma lipoprotein response to fluvastatin, a 3-hydroxy-3-methylglutanyl coen- zyme A (HMG-CoA) reductase inhibitor, has been reported (7). According to this study, subjects with the DD genotype had a greater reduction in plasma cholesterol, LDL-C and apoB levels com-