title: Association of intergenic polymorphism of organic anion transporter 1 and 3 genes with hypertension and blood pressure response to hydrochlorothiazide.
abstract: BACKGROUND
  Organic anion transporter (OAT) 1 and OAT3, encoded by a tightly linked gene pair, play a key role in renal secretion of diuretics. However, no study has yet examined the influence of OAT1 and OAT3 polymorphisms on high blood pressure (BP) and the response to thiazide diuretics. We hypothesized that intergenic polymorphisms between OAT1 and OAT3 might be associated with adult hypertension and the antihypertensive effects of hydrochlorothiazide (HCTZ).
  
  
  METHODS
  The association of an intergenic polymorphism (rs10792367) with hypertension risk was investigated in two independent case-control studies (n = 1,592 and 602), and then a combined analysis was performed for improving power (1,106 cases and 1,088 controls) with adjustment for geographic location. Two clinical trials (n = 542 and 274) were conducted in untreated hypertensive patients for the association of rs10792367 with antihypertensive responses to 4 and 8 weeks of HCTZ treatment.
  
  
  RESULTS
  No significant association was found between rs10792367 and hypertension after adjustment for conventional risk factors in either the two populations, respectively, or the combined two population. After adjustment for pretreatment BP and other confounders, HCTZ-induced reduction in systolic BP was 4.8 mm Hg (P = 0.006, first trial) and 6.1 mm Hg (P = 0.003, in second trial) lower, respectively, in C allele carriers than in GG carriers in the two clinical trials.
  
  
  CONCLUSIONS
  Intergenic polymorphism rs10792367 between OAT1 and OAT3 is not associated with hypertension, but appears to be involved in between-individual variations in antihypertensive responses to HCTZ.
authors.affiliation: Hypertension Division, Department of Cardiology, Cardiovascular Institute & Fuwai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
authors.forename: Yun-Feng
authors.initials: YF
authors.lastname: Han
authors.forename: Xiao-Han
authors.initials: XH
authors.lastname: Fan
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Hao
authors.initials: H
authors.lastname: Xue
authors.forename: Wei-Ju
authors.initials: WJ
authors.lastname: Li
authors.forename: Yi-Bo
authors.initials: YB
authors.lastname: Wang
authors.forename: Jing-Zhou
authors.initials: JZ
authors.lastname: Chen
authors.forename: Yi-Song
authors.initials: YS
authors.lastname: Zhen
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Zhang
authors.forename: Xianliang
authors.initials: X
authors.lastname: Zhou
authors.forename: Rutai
authors.initials: R
authors.lastname: Hui
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D016022:Case-Control Studies; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D027362:Organic Anion Transport Protein 1 / Q000235:genetics*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D000959:Antihypertensive Agents; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; C114338:organic anion transport protein 3; D006852:Hydrochlorothiazide