PHSS: Pharmacogenomics of Hydrochlorothiazide Sardinian Study

In 2014 we looked for variants associated with blood pressure response to hydrochlorothiazide over an 8-week follow-up by means of a genome-wide association analysis in of never-treated mild-to-moderate essential hypertensive patients: 343 samples from Sardinia, Italy, were analyzed in combination with 142 never treated essential hypertensives with the same characteristics enrolled in Milan (Northern Italy). Treatment with hydrochlorothiazide 25mg/day started after an 8 week run in period under standardized dietary regimen and complete diagnostic workout to confirm the presence of the disease and to exclude secondary hypertension. BP response to hydrochlorothiazide was evaluated after 4 and 8 weeks of treatment. The specificity of our findings for hydrochlorothiazide was confirmed in an independent cohort of essential hypertensive patients treated with losartan. Our best findings were also tested for replication in four independent hypertensive samples of European Ancestry. Long term follow-up: ongoing. Cardiac (ECHO), renal, metabolic phenotypes available. Serum, plasma, and urine samples are available. The primary CV outcome was combined CV/cerebrovascular events while secondary outcomes were atrial fibrillation, CKD, new onset of diabetes.

• Nicola Glorioso, Principal Investigator