RAS genetic variant may predict response to ARB

Researchers have identified a renin angiotensin system (RAS) genetic variant that independently predicts response to the angiotensin II receptor blocker (ARB) valsartan. "For the first time, a new possibility for personalized medicine has been shown in the treatment of hypertension with an ARB," reports Tadashi Konoshita, MD, Eiheiji, Fukui, Japan.

Dr. Konoshita and colleagues also found that systolic blood pressure and concomitant diabetes mellitus were independent predictors of which patients with hypertension were likely to respond to valsartan treatment. "Recent studies have proven favorable effects of ARBs on cardiovascular disorders," Dr. Konoshita says. "However, determinants of response to an ARB remain unclear."

Researchers studied 231 consecutive patients treated with 40 mg to 160 mg valsartan monotherapy daily for three months. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) assays were used to determine whether patients had one of five RAS genetic variants: renin (REN) C-5312T, ACE insertion/deletion (I/D), angiotensinogen M235T, AT1R A1166C, and AT2R C3123A.

At three months, researchers found significantly different changes in diastolic blood pressure between patients with CC versus CT/TT genotypes of REN C-5312T (10.7 mmHg vs 7.0 mmHg; p=0.02). Responder rates also differed between the CC and CT/TT genotypes (72.8% vs 58.0%, respectively; p=0.03).

Dr. Konoshito reports that the CC homozygote of REN C-5312T predicted response to valsartan with an odds ratio (OR) of 2.49, concomitant diabetes predicted response with an OR of 2.03, and systolic blood pressure predicted response to ARB treatment with an OR of 0.48. He adds that the study had 80% power to detect differences in response.