Genetic variation in renin predicts the effects of thiazide diuretics.
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).


METHODS
We enrolled nondiabetic hypertensive patients with a systolic blood pressure (SBP) ≥140 or a diastolic blood pressure (DBP) ≥90mmHg, who were either previously untreated or unsatisfactorily treated. After lifestyle modification and diet instruction for 2weeks, 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 (P=0·035), higher SBP (P=0·039), higher pulse pressure (P=0·006) and lower plasma REN activity (PRA) (P=0·020) when compared with the lower 1/3 responders. Renin rs11240688 CC polymorphism (β=9·931, corrected P=0·012), Log PRA (β=7·451, P=0·004) and baseline SBP (β=0·299, P=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.
Department of Medical Research and Education Division of Cardiology, Department of Medicine, Taipei, Taiwan.
Chin-Chou
CC
Huang
Chia-Min
CM
Chung
Shuen-Iu
SI
Hung
Hsin-Bang
HB
Leu
Tao-Cheng
TC
Wu
Po-Hsun
PH
Huang
Shing-Jong
SJ
Lin
Wen-Harn
WH
Pan
Jaw-Wen
JW
Chen
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D004232:Diuretics / Q000494:pharmacology*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012083:Renin / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics*; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology*
D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D012083:Renin