[Association of polymorphisms in ACE and CYP11B2 genes with antihypertensive effects of hydrochlorothiazide].
OBJECTIVE
To determine whether the blood pressure (BP) response to hydrochlorothiazide (HCTZ) was associated with the angiotensin converting-enzyme (ACE) I/D and aldosterone synthase (CYP11B2)-344T/C polymorphisms.


METHODS
The BP response to HCTZ 12.5 mg once daily for 6 weeks was assessed in 829 subjects with mild or moderate essential hypertension, and compared across the ACE and CYP11B2 genotypes.


RESULTS
Of the 829 enrolled subjects, 785 completed the study. The systolic BP response differed according to the ACE (DD 9.4 +/- 15.7 mm Hg, ID 4.8 +/- 16.3 mm Hg, and II 5.1 +/- 14.8 mm Hg, P < 0.01), but not the CYP11B2 genotype (P > 0.05). Subjects with the combination of ACE DD and CYP11B2 CC genotypes tended to have a more pronounced systolic BP reduction than the other genotypic combinations of these 2 genes. Multiple linear regression analyses showed that the ACE DD genotype and serum aldosterone concentration at baseline were associated with the systolic BP reduction after treatment. None of the genetic associations with changes in diastolic BP or mean arterial pressure reached statistical significance (P > 0.05).


CONCLUSIONS
The present study suggested that the ACE DD genotype was associated with the systolic BP response to HCTZ, and that the subjects with the combination of ACE DD and CYP11B2 CC genotypes might have a better BP response to HCTZ than the other genotypic combinations of these 2 genes.
Wu
Shou-ling
SL
The Affiliated Kailuan Hospital, North China Coal Medical College, Tangshan 063000, China. drliyun@163.com
Li
Yun
Y
Liu
Ke-jian
KJ
Hou
Guo-sheng
GS
Wang
Jian-jun
JJ
Wu
Yun-Tao
YT
Song
Shao-min
SM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics*; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use*
D049993:Sodium Chloride Symporter Inhibitors; D006852:Hydrochlorothiazide; D019405:Cytochrome P-450 CYP11B2; D007703:Peptidyl-Dipeptidase A