GENRES: GENes and Antihypertensive Drug RESponse

GENRES is a prospective, single center, randomized, double-blind, cross-over, placebo-controlled clinical trial conducted in 237 moderately hypertensive Finnish men aged 35 to 60 years. Four antihypertensive drugs from four different classes were given to each participant as monotherapy for 4 weeks in a random order, with a placebo washout before and between the treatment periods (hydrochlorothiazide 25mg, bisoprolol 5mg, amlodipine 5mg, and losartan 50 mg). Responses were assessed with 24-h ambulatory and office blood pressure measurements and analyzed according to clinical parameters (e.g. age, BMI, duration of hypertension, etc).

Baseline clinical and laboratory parameters could to some extent be used to predict the efficacy of antihypertensive therapies. Accordingly, a negative correlation was found between total serum calcium concentration and blood pressure response to amlodipine, while plasma renin activity correlated positively with blood pressure response to losartan and bisoprolol but negatively with response to hydrochlorothiazide. Data on plasma glucose, insulin, total cholesterol, LDL, HDL, triglyceride, uric acid, potassium, sodium, creatinine, aldosterone and renin levels are all available for further studies.

This trial should provide an excellent platform for future pharmacogenetic analyses on antihypertensive drug responsiveness. Initial GWAS studies, supplemented with data from other ICAPS groups, provide evidence for a variant in the nephrin gene influencing losartan response and two other gene loci (ALDH1A3, CLIC5) influencing hydrochlorothiazide response.

• Kimmo Kontula, University of Helsinki, Principal Investigator
• Timo Hiltunen, University of Helsinki
• Kati Donner, University of Helsinki