Effects of ACE and ADD1 gene polymorphisms on blood pressure response to hydrochlorothiazide: a meta-analysis

Hydrochlorothiazide (HCTZ) is used to treat uncomplicated hypertension. However, many studies have reported the variance of inter-individual response to HCTZ. A meta-analysis of published data was conducted to evaluate the pharmacogenetic associations of ACE I/D and ADD1 Gly460Trp polymorphisms with blood pressure changes during HCTZ therapy. To analyze the influence of ACE I/D polymorphism, 4 studies including 1,439 patients were assessed and the 3 genotypes were compared (II vs. ID, II vs. DD, and ID vs. DD) with respect to blood pressure changes. A significant association between ACE and blood pressure change was observed for the comparison of the II and DD (standard differences in means = 0.256; 95% CI, 0.109 - 0.403). For ADD1 Gly460Trp polymorphism, 4 studies including 1,001 patients were assessed, and GlyGly vs. GlyTrp, GlyGly vs. TrpTrp and GlyTrp vs. TrpTrp genotype comparisons were analyzed. A significant association between ADD1 and blood pressure change was observed for the comparisons of GlyGly vs. GlyTrp (standard differences in means= 2.78; 95% CI, 0.563 - 4.99) and GlyGly vs. TrpTrp (standard differences in means = 1.80; 95% CI, 1.38 - 2.22). This study is the first meta-analysis to evaluate the influences of ACE and ADD1 polymorphisms on blood pressure responses to HCTZ to combine the inconsistent results of previous studies.