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- Title
Genetic Variant of the Renin-Angiotensin System and Diabetes Influences Blood Pressure Response to Angiotensin Receptor Blockers.
- Authors
Konoshita, Tadashi; Kato, Norihiro; Fuchs, Sébastien; Mizuno, Shinichi; Aoyama, Chikako; Motomura, Makoto; Makino, Yasukazu; Wakahara, Shigeyuki; Inoki, Isao; Miyamori, Isamu; Pinet, Florence
- Abstract
OBJECTIVE-- Recent studies have proven the favorable effects of angiotensin receptor blockers (ARBs) on cardiovascular and renal disorders. However, determinants of the response to ARBs remain unclear. We substantiated the hypothesis that genetic variants of the reninangiotensin system (RAS) have significant impacts on the response to ARBs. RESEARCH DESIGN AND METHODS-- Subjects comprised 231 consecutively enrolled hypertensive individuals including 45 type 2 diabetic subjects. Five genetic variants of the RAS, i.e., renin (REN) C-5312T, ACE insertion/deletion, angiotensinogen M235T, angiotensin 11 type 1 receptor A1166C, and angiotensin 11 type 2 receptor C3123A were assayed by PCR and restriction fragment-length polymorphism. A dose of 40-160 mg/day of valsartan was administered for 3 months as a monotherapy. RESULTS-- Changes in diastolic blood pressure significantly differed between genotypes of REN C-5312T: 10.7-mmHg reduction (from 95.9 + 12.9 to 85.2 ± 11.4) in CC versus 7.0mmHg reduction (from 94.7 ± 14.0 to 87.7 ± 12.6) in CT/TT (P = 0.02 for interactive effects of valsartan and genotype). Responder rates also differed between the genotypes: 72.8% in CC versus 58.0% in CT/TT (P = 0.03). Univariate analysis indicated a significant association of response to valsartan with blood pressure, diabetes, plasma aldosterone concentration, and CC homozygotes of PEN C-5312T. Finally, multiple logistic regression analysis revealed that systolic blood pressure, CC homozygotes of REN C-5312T, and diabetes were independent predictors for responders with odds ratios (95% CI) of 2.49 (1.41-4.42), 2.03 (1.10-3.74), and 0.48 (0.24-0.96), respectively. CONCLUSIONS-- This study provides strong support that a genetic variant of REN C-5312T and diabetes contribute to the effects of ARBs and are independent predictors for responder. Thus, in treatment of hypertension with ARBs, a new possibility for personalized medicine has been shown.
- Subjects
RENIN-angiotensin system; DIABETES; ANGIOTENSINS; PATIENTS; HYPERTENSION; PEOPLE with diabetes; VALSARTAN; ALDOSTERONE
- Publication
Diabetes Care, 2009, Vol 32, Issue 8, p1485
- ISSN
0149-5992
- Publication type
Article
- DOI
10.2337/dc09-0348