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. 2015 Nov;33(11):2278-85.
doi: 10.1097/HJH.0000000000000714.

PTPRD Gene Associated With Blood Pressure Response to Atenolol and Resistant Hypertension

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Free PMC article

PTPRD Gene Associated With Blood Pressure Response to Atenolol and Resistant Hypertension

Yan Gong et al. J Hypertens. .
Free PMC article

Abstract

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.

Conflict of interest statement

Conflicts of interest

Y.G., R.M.C., A.L.B., A.B.C., J.G.G., E.B., S.T.T., and J.A.J. received funding from NIH. J.G.G. is a consultant for Boehringer-Ingelheim. E.B. received honoraria from the Foundation of Rome. Other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Blood pressure response by genotype for the single-nucleotide polymorphisms near the OTOL1 gene on chromosome 3 in the pharmacogenomic evaluation of antihypertensive responses participants. (a) rs7640608 in white participants. (b) rs12486357 in black participants. Error bars represent standard error of the means.
FIGURE 2
FIGURE 2
Regional plots for single-nucleotide polymorphism (SNPs) in the chromosome 9p23 region near PTPRD gene associated with DBP response to atenolol in pharmacogenomic evaluation of antihypertensive responses in white (a, top SNPs: rs12346562 and rs1104514) and black participants (b, top SNP: rs10739150) and SNPs associated with resistant hypertension in INVEST-GENES in the meta-analysis of whites, Hispanics, and blacks hypertensive patients with coronary artery disease (c, top SNP: rs4742610). INVEST-GENES, international verapamil SR trandolapril study genetic substudy.
FIGURE 3
FIGURE 3
Blood pressure response by genotype for the single-nucleotide polymorphisms near the PTPRD gene on chromosome 9p23 in pharmacogenomic evaluation of antihypertensive responses participants. (a) rs12346562 in white participants. (b) rs10739150 in black participants. Error bars represent standard error of the means.

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