Essential hypertension is a multifactorial disease caused by the interaction of environmental factors with specific genotypes of multiple genes. It is characterized by inter-individual variability in drug responsiveness. According to the previous studies, thiazide diuretics and calcium channel blockers are effective, as well as combinations that include renin-angiotensin-aldosterone system blockers in reducing BP. To identify the genetic determinants of the antihypertensive and adverse metabolic responses to thiazide diuretics and beta blockers, the study of candidate genes involved in sodium transport systems (ADD1,GNB3,SLC12A3) and ion regulation systems (ATP2A2,PRKWNK1,PRKWNK4) will be done. Individuals with uncomplicated hypertension (n=500), ages 18 to 65 years of Punjabi population of India will be enrolled in this study. Genotyping will be done with PCR-RFLP method and further drug- gene interactions will be studied. Pharmacogenetic guided therapy will add substantially to our understanding of genetic determinants of antihypertensive and adverse metabolic responses to commonly used antihypertensive drug classes. The pharmacodynamics (drug target/ receptor and post- receptor level) study of genetic determinants of drug responses is likely to allow us to more precise therapy to individual patients.
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