SOPHIA: Pharmacogenomics of Losartan

This genome-wide association study aimed to identify genetic polymorphisms regulating blood pressure response to the angiotensin II receptor blocker, losartan in 372 never treated, mild-to-moderate essential hypertensives. The recruitment was made both in the Mainland of Italy and in Sardinia: all participants were genotyped (GWAS).

Participants received study drug losartan 50 mg/day 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. 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.

The findings were tested in two replication cohorts, GERA 2 and GENRES: the association of BP response to losartan with CAMK1D gene as a novel locus associated with blood pressure response to losartan was replicated in GENRES. Our findings may represent a useful tool to personalize the treatment of essential hypertension.

• Nicola Glorioso, Principal Investigator