MIHYPHCTZ: Milan Hypertension Pharmacogenomics of HCTZ
The characteristics of MIHYPHCTZ cohort (newly discovered participants with primary hypertension) allow to avoid structural changes associated with long lasting hypertension that can mask the characteristic genotype–phenotype relationship causing the initial development of hypertension and the response to drug. Moreover including only never-treated patients which allowed for avoidance of withdrawal effects (the rate of returning BP to pretreatment levels may vary between 1 month–1 year).
MIHYPHCTZ is a cohort of 220 European Americans newly discovered and never-treated participants with primary hypertension (defined by mean of three consecutive measurements of office SBP > 140 or DBP > 90 mmHg) enrolled after exclusion of secondary hypertension and a 1-month controlled diet (150 mmol sodium daily) run-in period. Patients were treated for 8 weeks with HCTZ, at a dose of 12.5 mg daily for 4 weeks and 25 mg daily for 4 further weeks. Before starting treatment, blood for chemistry, baseline plasma renin activity, aldosterone and urinary samples were collected.
A genome-wide association meta-analyses was conducted. Participants were from the Pharmacogenomic Evaluation of Antihypertensive Response study and the Genetic Epidemiology of Response to Antihypertensive study. The associated polymorphisms with blood pressure response that were found were replicated in independent samples of hydrochlorothiazide-treated European hypertensives. Two novel loci replicated for same-direction association of BP response: rs16960228 and rs2273359.