ORIGINAL INVESTIGATIONS Insertion/Deletion Polymorphism in Intron 16 of the ACE Gene and Left Ventricular Hypertrophy in Patients With End-Stage Renal Disease Eiichi Osono, MD, Satoshi Kurihara, MD, Naoaki Hayama, MD, Yusei Sakurai, MD, Kazuhiro Ohwada, MD, Noritaka Onoda, MD, Masato Takeuchi, MD, Tamami Tomizawa, MD, Yuichi Komaba, MD, Kazumasa Hashimoto, MD, Seiichi Matsunobu, MD, Hideo Yoneshima, MD, and Yasuhiko Iino, MD ● We studied the relationship between polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene and left ventricular (LV) hypertrophy in uremic patients treated with hemodialysis therapy. The LV parameters were not different for age-, hematocrit-, and blood pressure–matched patients in DD, ID, and II genotype groups. The most important factor for LV hypertrophy was systolic blood pressure, which correlated with the posterior wall thickness (r  0.35; P  0.001) and LV mass index (LVMI; r  0.23; P  0.032). Among nonhypertensive patients, the frequency of interventricular septum (IVS) hypertrophy (G12 mm) and hypertrophy in LVMI (G145 g/m 2 ) was significantly greater in patients with the DD genotype than in I allele–positive () patients. The odds rate for IVS hypertrophy was 5.04 (95% confidence interval, 1.15 to 24.8). These data suggest that the DD genotype of the ACE gene polymorphism is a contributory factor for the development of LV hypertrophy in patients with end-stage renal disease (ESRD).  1998 by the National Kidney Foundation, Inc. INDEX WORDS: Angiotensin-converting enzyme; left ventricular wall thickness; I/D polymorphism; dialysis. I N PATIENTS WITH end-stage renal disease (ESRD), left ventricular (LV) hypertrophy occurs frequently 1-3 and is associated with mor- bidity and mortality. 4-6 The pathogenesis of LV hypertrophy has been discussed; hypertension, 1,7,8 anemia, 2,7 age, 1,7 and secondary hyperparathy- roidism 9 are implicated as risk factors for its development among these patients. Although the number of patients with severe anemia was re- duced by treatment with recombinant human erythropoetin, we observed many normotensive patients with LV hypertrophy. Renin-angiotensin systems, particularly the lo- cal renin-angiotensin system in the cardium, are associated with cardiac cell growth and LV hyper- trophy. 10,11 Angiotensin I–converting enzyme (ACE) inhibitors reduce the extent of LV hyper- trophy 12,13 independent of blood pressure regula- tion. An insertion (I)/deletion (D) polymorphism in intron 16 of the ACE gene, when homozygous for the D allele (DD genotype), is linked with plasma 14-16 or cardiac 17 ACE activities and asso- ciated with LV hypertrophy in patients with hypertension. 18,19 These findings indicated the possibility that the I/D polymorphism of the ACE gene may also be an independent risk factor for the development of LV hypertrophy among pa- tients with ESRD. In this study, we undertook to determine the relationship between the ACE gene polymorphism and LV wall thickness in uremic patients treated with hemodialysis therapy. PATIENTS AND METHODS Before this study, we studied the I/D polymorphism in intron 16 of the ACE gene for 276 patients who received hemodialysis therapy in our hospital. The DD genotype of the ACE gene was observed in 33 patients, the ID genotype in 130 patients, and the II genotype in 113 patients. The frequency of the D allele was similar to that observed in other studies of Japanese subjects. 16,19,20 In this study, pa- tients with cardiac valvular disease and inadequate echocar- diographic images were excluded. The coordinators, who were not directly concerned with these patients, selected 30 patients from each genotype group, matched for age, sex, duration of dialysis therapy, and number of patients with diabetic nephropathy (Table 1). These 90 patients were From the Department of Nephrology and Cardiology, Kasukabe Shuwa Hospital, Saitama; and the Department of Second Internal Medicine, Nippon Medical School, Tokyo, Japan. Received October 31, 1997; accepted in revised form May 22, 1998. Supported in part by the Annual Foundation for Private Schools, for E.O., Tokyo, Japan. Address reprint requests to Eiichi Osono, Dept of Neph- rology, 2nd Internal Medicine, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo, Japan 113. E-mail: osono@ ksh.smds.co.jp  1998 by the National Kidney Foundation, Inc. 0272-6386/98/3205-0004$3.00/0 American Journal of Kidney Diseases, Vol 32, No 5 (November), 1998: pp 725-730 725