与阿替洛尔的血压反应及顽固性高血压相关的PTPRD基因。
PTPRD gene associated with blood pressure response to atenolol and resistant hypertension.
作者信息
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
机构信息
aDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida, Gainesville, Florida USA bDepartment of Medicine and Program in Personalized and Genomic Medicine, University of Maryland, Baltimore, Maryland, USA cDepartment of Medicine, University of Helsinki, and University Central Hospital of Helsinki, Helsinki, Finland dBHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK eDepartment of Community Health and Family Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA fInstitute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland. gCollege of Medicine, Mayo Clinic Rochester, Rochester, Minnesota USA hCenter for Human Genetics, University of Texas at Houston, Houston, Texas, USA iRIKEN Center for Integrative Medical Sciences, Yokohama, Japan jSchool of Medicine, Emory University, Atlanta, Georgia, USA kDivision of Cardiovascular Medicine, College of Medicine, University of Florida, Gainesville, Florida, USA.
出版信息
J Hypertens. 2015 Nov;33(11):2278-85. doi: 10.1097/HJH.0000000000000714.
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.
目的
本研究旨在识别影响血压（BP）对β受体阻滞剂阿替洛尔反应的单核苷酸多态性（SNP）。
方法
在抗高血压反应的药物基因组学评估研究中，对233名患有单纯性高血压的白人参与者进行了阿替洛尔单药治疗的血压反应全基因组关联分析。在四组独立的高血压个体（共n = 2114）中验证了42个与阿替洛尔单药治疗的舒张期或收缩期反应相关且P值小于10的多态性。
结果
在白人中，PTPRD基因附近的两个多态性（rs12346562和rs1104514）与阿替洛尔的舒张压反应相关（分别为P = 3.2×10和P = 5.9×10），而在另一组228名白人中，对氢氯噻嗪的反应呈方向相反的关联（P = 0.0018和P = 0.00012）。PTPRD附近的另一个多态性（rs10739150）与150名黑人高血压个体对阿替洛尔的反应相关（P = 8.25×10）。在原发性高血压药物反应遗传学研究中，rs12346562在207名芬兰男性中与对比索洛尔（另一种β受体阻滞剂）的反应有类似的关联趋势。此外，在国际维拉帕米缓释片群多普利研究中，PTPRD基因的一个内含子单核苷酸多态性（rs4742610）与白人和西班牙裔的顽固性高血压相关（荟萃分析P = 3.2×10）。
结论
PTPRD被确定为一个新的位点，可能与多个种族对阿替洛尔的血压反应和顽固性高血压相关。
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