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Keywords:

  • Blood pressure;
  • hydrochlorothiazide;
  • hypertension;
  • renin;
  • single nucleotide polymorphism

Eur J Clin Invest 2011; 41 (8): 828–835

Abstracts

Background  While genetic variants of renin-angiotensin-aldosterone system (RAAS) may modify the blood pressure (BP) response to thiazide diuretics, there was no evidence of genetic variations in renin (REN) playing a role. This study aimed to address the potential effects of genetic variations of RAAS on the response to initial treatment of hydrochlorothiazide (HCTZ).

Materials and methods  We enrolled nondiabetic hypertensive patients with a systolic blood pressure (SBP) ≥ 140 or a diastolic blood pressure (DBP) ≥ 90 mmHg, who were either previously untreated or unsatisfactorily treated. After lifestyle modification and diet instruction for 2 weeks, 90 patients with persistently elevated BP were given HCTZ 50 mg every morning for 2 weeks. Single nucleotide polymorphism markers were selected from genes involving in RAAS, including rs7079 and rs699 of angiotensinogen, rs4293 and rs4353 of angiotensin-converting enzyme and rs1464816 and rs11240688 of REN.

Results  The patients were divided into three groups according to the SBP response after HCTZ. The upper 1/3 responders had older age (= 0·035), higher SBP (= 0·039), higher pulse pressure (P = 0·006) and lower plasma REN activity (PRA) (= 0·020) when compared with the lower 1/3 responders. Renin rs11240688 CC polymorphism (β = 9·931, corrected = 0·012), Log PRA (β = 7·451, = 0·004) and baseline SBP (β = 0·299, = 0·006) were the independent predictors for the BP lowering response.

Conclusions  In addition to PRA, renin rs11240688 CC polymorphism may also independently predict the effect of HCTZ.