Key result
The REN C-5312T CC genotype was an independent predictor of blood pressure response to valsartan in hypertensive patients, doubling the odds of being a responder compared to the CT/TT genotype (OR 2.03).
Why the study?
Does valsartan reduce blood pressure differently based on genetic variants of the renin-angiotensin system and diabetes in hypertensive individuals?
Observational (n=231)
No
Does valsartan reduce blood pressure differently based on genetic variants of the renin-angiotensin system and diabetes in hypertensive individuals?
The REN C-5312T genetic variant and diabetes independently predict the blood pressure response to valsartan in hypertensive patients, suggesting a role for personalized medicine.
Answers are grounded in this paper and cite their sources.
May support pharmacogenetic testing for valsartan response; leaves open need for randomized validation in hypertension.
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 renin-angiotensin 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 II type 1 receptor A1166C, and angiotensin II 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 7.0-mmHg 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 REN 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.
No takes yet. Share an insight, caveat, or question.
Konoshita et al. (2009) conducted an observational in Hypertension (n=231). REN C-5312T CC genotype vs. REN C-5312T CT/TT genotype was evaluated on Responder to valsartan (decrease in diastolic blood pressure ≥5 mmHg) (OR 2.03, 95% CI 1.10-3.74, p=0.02). The REN C-5312T CC genotype was an independent predictor of blood pressure response to valsartan in hypertensive patients, doubling the odds of being a responder compared to the CT/TT genotype (OR 2.03).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: