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Войти в исследования Journal of hypertension · 2015
PTPRD gene associated with blood pressure response to atenolol and resistant hypertension.
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Gong Yan, McDonough Caitrin W, Beitelshees Amber L, El Rouby Nihal, Hiltunen Timo P, O'Connell Jeffrey R, Padmanabhan Sandosh, Langaee Taimour Y, Hall Karen, Schmidt Siegfried O F, Curry Robert W, Gums John G, Donner Kati M, Kontula Kimmo K, Bailey Kent R, Boerwinkle Eric, Takahashi Atsushi, Tanaka Toshihiro, Kubo Michiaki, Chapman Arlene B, Turner Stephen T, Pepine Carl J, Cooper-DeHoff Rhonda M, Johnson Julie A
Аннотация
OBJECTIVE: The aim of this study is to identify single-nucleotide polymorphisms (SNPs) influencing blood pressure (BP) response to the β-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 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 and P = 5.9 × 10, 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 = 8.25 × 10). rs12346562 had a similar trend in association with response to bisoprolol (a different β-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 = 3.2 × 10).
CONCLUSION: PTPRD was identified as a novel locus potentially associated with BP response to atenolol and resistant hypertension in multiple ethnic groups.
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 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 and P = 5.9 × 10, 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 = 8.25 × 10). rs12346562 had a similar trend in association with response to bisoprolol (a different β-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 = 3.2 × 10).
CONCLUSION: PTPRD was identified as a novel locus potentially associated with BP response to atenolol and resistant hypertension in multiple ethnic groups.