title: Tagging SNPs in REN, AGTR1 and AGTR2 genes and response of renin activity, angiotensin II and aldosterone concentrations to antihypertensive treatment in Kazakans.
abstract: OBJECTIVE
  Polymorphisms of REN, AGTR1 and AGTR2 may be associated with responses of renin-angiotensin-aldosterone system (RAAS) activity phenotypes to angiotensin-converting enzyme inhibitor (ACEI) antihypertensive treatment.
  
  
  METHODS
  A total of 400 first diagnosed Kazak hypertensives were randomly allocated to two groups and received a 3-week course of either captopril and atenolol as monotherapy under double blinding. Genotype-phenotype association analyses were performed by covariance analyses between baseline level and responses of blood pressure, renin, angiotensin II and aldosterone concentrations with tagging single nucleotide polymorphisms (SNPs) in REN, AGTR1 and AGTR2 genes. A false discovery rate method was used to adjust multiple testing.
  
  
  RESULTS
  After adjustment for multiple testing, we found that the G allele of rs6676670 (T/G) in intron 1 of REN was significantly associated with higher baseline aldosterone concentrations (p < 0.0001, explained variance (EV) = 2.3%). Significant associations after adjustments were also found between the A allele of rs2887284, with higher baseline renin activity (p = 0.022, EV = 1.0%), higher responses of renin (p = 0.018 EV = 5.4%), and higher responses of angiotensin II (p = 0.0255, EV = 3.13%) to the treatment of ACEI. The carriers of the A allele of rs2887284 appeared to be more sensitive to the ACEI treatment.
  
  
  CONCLUSIONS
  rs2887284 in intron 9 of REN is associated with the response of renin and angiotensin II levels to ACEI treatment.
authors.affiliation: Pediatric Institute, Children's Hospital of Fudan University, Shanghai, China. 01.weili@gmail.com
authors.forename: Weili
authors.initials: W
authors.lastname: Yan
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zimei
authors.initials: Z
authors.lastname: Shan
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Yongdi
authors.initials: Y
authors.lastname: Huang
authors.forename: Chenchen
authors.initials: C
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Yan
mesh_terms: D000450:Aldosterone / Q000097:blood*; D000804:Angiotensin II / Q000097:blood*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use; D001794:Blood Pressure; D002216:Captopril / Q000627:therapeutic use; D002681:China; D004311:Double-Blind Method; D005006:Ethnicity / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics*; D012083:Renin / Q000097:blood / Q000235:genetics*
chemical_list: C544065:AGTR1 protein, human; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D000450:Aldosterone; D001262:Atenolol; D002216:Captopril; D012083:Renin