title: Hypertension associated polymorphisms in WNK1/WNK4 are not associated with hydrochlorothiazide response.
abstract: OBJECTIVE
  Our purpose was to investigate whether with-no-K[Lys] kinase (WNK) 1 and WNK4 genetic polymorphisms are associated with both hypertension and diuretics response.
  
  
  METHODS
  Two WNK1 and one WNK4 polymorphisms were detected in two independent populations (n = 1592 and 602) for association with hypertension, and in two clinical trials of hydrochlorothiazide treatment (n = 542 and 274) for association with diuretics response.
  
  
  RESULTS
  Two polymorphisms were found to be associated with hypertension risk with odds ratio of 1.55 for WNK1 rs1468326 (P<0.001) and 1.88 for WNK4 rs9916754 (P<0.001) in the first population, and 1.54 for WKN1 rs1468326, and 1.82 for WNK4 rs9916754 in the second population. However, two clinical trials found no relationship between these WNK polymorphisms and systolic/diastolic blood pressure responses to 4 or 8 weeks treatment of hydrochlorothiazide.
  
  
  CONCLUSIONS
  Our findings suggest that hypertension associated polymorphisms in WNK1 and WNK4 may not be predictors for antihypertensive response to diuretics.
authors.affiliation: Department of Geriatrics, The Military General Hospital of Beijing PLA, Beijing, China; Hypertension Division, Department of Cardiology, Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Han
authors.affiliation: Hypertension Division, Department of Cardiology, Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: XiaoHan
authors.initials: X
authors.lastname: Fan
authors.affiliation: Key Laboratory for Clinical Cardiovascular Genetics, Ministry of Education & Sino-German Laboratory for Molecular Medicine, Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.affiliation: Key Laboratory for Clinical Cardiovascular Genetics, Ministry of Education & Sino-German Laboratory for Molecular Medicine, Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory for Clinical Cardiovascular Genetics, Ministry of Education & Sino-German Laboratory for Molecular Medicine, Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Yibo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory for Clinical Cardiovascular Genetics, Ministry of Education & Sino-German Laboratory for Molecular Medicine, Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Jingzhou
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory for Clinical Cardiovascular Genetics, Ministry of Education & Sino-German Laboratory for Molecular Medicine, Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Yisong
authors.initials: Y
authors.lastname: Zhen
authors.affiliation: Key Laboratory for Clinical Cardiovascular Genetics, Ministry of Education & Sino-German Laboratory for Molecular Medicine, Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China.
authors.forename: Weili
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Hypertension Division, Department of Cardiology, Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China; Key Laboratory for Clinical Cardiovascular Genetics, Ministry of Education & Sino-German Laboratory for Molecular Medicine, Cardiovascular Institute & FuWai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Electronic address: huirutai@sglab.org.
authors.forename: Rutai
authors.initials: R
authors.lastname: Hui
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D002681:China; D004232:Diuretics / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000076204:WNK Lysine-Deficient Protein Kinase 1
chemical_list: D000959:Antihypertensive Agents; D004232:Diuretics; D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D006852:Hydrochlorothiazide; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498743:WNK1 protein, human; C433806:WNK4 protein, human