Pharmacogenomics of Beta-blockers

Aim: Pharmacogenomics seeks for genetic predictors of drug response. Aim of this study is to look for gene variations associated with blood pressure response to beta-blockers.Methods: 403 (M=46.9%; F=53.1%; mean age 51.7±11.4yrs) untreated Sardinian hypertensive patients were enrolled at the Hypertension Center, University of Sassari. A 8-weeks follow-up to assess the presence of the disease and secondary hypertension. Genomic DNA was extracted from the peripheral blood collected at week 0 (start treatment with atenolol 50mg b.i.d).Results: statistically significant differences between baseline and the first follow-up at 4-weeks of treatment are reported. Systolic pressure varied significantly after 4 weeks of treatment: mean values 159±15 mmHg (baseline) vs. 136±17 mmHg (4-weeks). 431 SNPs has been identified: out of these, 183 showed significant delta-SBP4; a similar set of analysis has been conducted with regard to delta-DBP and heart rate. Then we have conducted a review of functional mapping of each gene polymorphism to highlight a possible relationship between these genes and their functional pathways directly or indirectly involved in the regulation of blood pressure. Some genes found have shown a physiological mechanisms involved in blood pressure regulation.Conclusion: Our preliminary data identified several genes involved in the response to antihypertensive drug treatment: theses findings could allow new gene-targeted treatments.