Objective: The aim of this study is to identify singlenucleotide polymorphisms (SNPs) influencing blood pressure (BP) response to the b-blocker atenolol. Methods: Genome-wide association analysis of BP response to atenolol monotherapy was performed in 233 white participants with uncomplicated hypertension in the pharmacogenomic evaluation of antihypertensive responses study. Forty-two polymorphisms with P less than 10-5 for association with either diastolic or systolic response to atenolol monotherapy were validated in four independent groups of hypertensive individuals (total n=2114). Results: In whites, two polymorphisms near the gene PTPRD (rs12346562 and rs1104514) were associated with DBP response to atenolol (P=3.2.10-6 and P=5.9.10-6, respectively) with directionally opposite association for response to hydrochlorothiazide in another group of 228 whites (P=0.0018 and P=0.00012). A different polymorphism (rs10739150) near PTPRD was associated with response to atenolol in 150 black hypertensive individuals (P=8.2510-6). rs12346562 had a similar trend in association with response to bisoprolol (a different b-blocker) in 207 Finnish men in the genetics of drug responsiveness in essential hypertension study. In addition, an intronic single-nucleotide polymorphism (rs4742610) in the PTPRD gene was associated with resistant hypertension in whites and Hispanics in the international verapamil SR trandolapril study (meta-analysis P=3.210-5). Conclusion: PTPRD was identified as a novel locus potentially associated with BP response to atenolol and resistant hypertension in multiple ethnic groups.
All Science Journal Classification (ASJC) codes
- Internal Medicine
- Cardiology and Cardiovascular Medicine