OBJECTIVE: To evaluate the effect of CYP11B2 gene -344T/C polymorphism on renin-angiotensin-aldosterone system (RAAS) activity and blood pressure in response to hydrochlorothiazide (HCTZ) treatment in Han Chinese patients with essential hypertension. METHODS:Eight hundred and twenty-nine patients with mild/moderate essential hypertensive were enrolled. All subjects had their antihypertensive medications withdrawn. After two weeks of wash-out period with placebo, each patient was given 12.5 mg of HCTZ per day for the next six weeks. Physical, biochemical measurements, and the activity of RAAS were taken at the end of the wash-out period (baseline) and 6-week diuretic therapy period. Changes in systolic and diastolic blood pressure were analyzed for association with interaction between genotypes at CYP11B2 -344T/C polymorphism and gender. RESULTS: A total of 776 patients completed the study. 17.5% of subjects have achieved blood pressure normalization after six weeks treatment. For male patients, the aldosterone level with CC genotype was significantly higher than that of those with TT or TC genotype. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was less obvious than that in others, whilst the increase of aldosterone level was greater. For female patients, no association was found between CYP11B2 -344T/C polymorphism and aldosterone level. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was greater than others, whilst the increase of aldosterone activity was less apparent. CONCLUSION: In males, the -344T/C polymorphism of CYP11B2 gene is associated with aldosterone level, and the change of aldosterone level was greater, the blood pressure response was weaker after HCTZ treatment. In females, there was no association between this polymorphism and aldosterone level. The change of aldosterone level and blood pressure response to HCTZ were different from that in males.
RCT Entities:
OBJECTIVE: To evaluate the effect of CYP11B2 gene -344T/C polymorphism on renin-angiotensin-aldosterone system (RAAS) activity and blood pressure in response to hydrochlorothiazide (HCTZ) treatment in Han Chinese patients with essential hypertension. METHODS: Eight hundred and twenty-nine patients with mild/moderate essential hypertensive were enrolled. All subjects had their antihypertensive medications withdrawn. After two weeks of wash-out period with placebo, each patient was given 12.5 mg of HCTZ per day for the next six weeks. Physical, biochemical measurements, and the activity of RAAS were taken at the end of the wash-out period (baseline) and 6-week diuretic therapy period. Changes in systolic and diastolic blood pressure were analyzed for association with interaction between genotypes at CYP11B2-344T/C polymorphism and gender. RESULTS: A total of 776 patients completed the study. 17.5% of subjects have achieved blood pressure normalization after six weeks treatment. For male patients, the aldosterone level with CC genotype was significantly higher than that of those with TT or TC genotype. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was less obvious than that in others, whilst the increase of aldosterone level was greater. For female patients, no association was found between CYP11B2-344T/C polymorphism and aldosterone level. Following the HCTZ treatment, the blood pressure response in patients with CC genotype was greater than others, whilst the increase of aldosterone activity was less apparent. CONCLUSION: In males, the -344T/C polymorphism of CYP11B2 gene is associated with aldosterone level, and the change of aldosterone level was greater, the blood pressure response was weaker after HCTZ treatment. In females, there was no association between this polymorphism and aldosterone level. The change of aldosterone level and blood pressure response to HCTZ were different from that in males.
Authors: A A Seyerle; C M Sitlani; R Noordam; S M Gogarten; J Li; X Li; D S Evans; F Sun; M A Laaksonen; A Isaacs; K Kristiansson; H M Highland; J D Stewart; T B Harris; S Trompet; J C Bis; G M Peloso; J A Brody; L Broer; E L Busch; Q Duan; A M Stilp; C J O'Donnell; P W Macfarlane; J S Floyd; J A Kors; H J Lin; R Li-Gao; T Sofer; R Méndez-Giráldez; S R Cummings; S R Heckbert; A Hofman; I Ford; Y Li; L J Launer; K Porthan; C Newton-Cheh; M D Napier; K F Kerr; A P Reiner; K M Rice; J Roach; B M Buckley; E Z Soliman; R de Mutsert; N Sotoodehnia; A G Uitterlinden; K E North; C R Lee; V Gudnason; T Stürmer; F R Rosendaal; K D Taylor; K L Wiggins; J G Wilson; Y-Di Chen; R C Kaplan; K Wilhelmsen; L A Cupples; V Salomaa; C van Duijn; J W Jukema; Y Liu; D O Mook-Kanamori; L A Lange; R S Vasan; A V Smith; B H Stricker; C C Laurie; J I Rotter; E A Whitsel; B M Psaty; C L Avery Journal: Pharmacogenomics J Date: 2017-07-18 Impact factor: 3.550