title: Rs495828 polymorphism of the ABO gene is a predictor of enalapril-induced cough in Chinese patients with essential hypertension.
abstract: OBJECTIVE
  ABO genetic polymorphisms have recently been associated with angiotensin-converting enzyme (ACE) activity and inflammation, which play a critical role in the pathogenic mechanism of ACE inhibitor-induced cough. Therefore, the current study determined the association of ABO genetic polymorphisms with enalapril-induced cough in Chinese patients with essential hypertension.
  
  
  METHODS
  A total of 450 essential hypertensive patients treated with 10 mg of enalapril maleate were genotyped for ABO genetic polymorphisms using the PCR-direct sequencing method. Cough was recorded when patients were bothered by cough and respiratory symptoms during enalapril treatment without an identifiable cause.
  
  
  RESULTS
  The distribution of rs8176740 and rs495828 was different between the coughers and the controls [P=0.039; odds ratio (OR)=0.70, P=0.018; OR=1.41]. The risk of enalapril-induced cough in the rs495828 TT carriers was increased (P=0.008; OR=2.69), which remained significant after false discovery rate correction. The results for the rs8176740 polymorphism were significant in the female subgroup (P=0.027; OR=0.22). Haplotype analysis of the four ABO polymorphisms (rs8176746/rs8176740/rs495828/rs12683493) showed that the frequency of the GATC haplotype was higher in the coughers than those in the controls (26.6 vs. 18.8%, P=0.033; OR=1.43).
  
  
  CONCLUSIONS
  The rs495828 polymorphism was associated with enalapril-induced cough and may serve as a useful pharmacogenomics marker of the safety of enalapril in Chinese patients with essential hypertension. The mechanism for the associations may involve the effects of the ABO gene or ABO blood type on ACE activity and inflammation.
authors.affiliation: aPharmacogenetics & Pharmacogenomics Research Institute, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital, Central South University, Changsha, Hunan bDepartment of Cardiology, People's Hospital, Peking University, Beijing cSchool of Health Administration, Anhui Medical University, Hefei, People's Republic of China.
authors.forename: Jian-Quan
authors.initials: JQ
authors.lastname: Luo
authors.forename: Fa-Zhong
authors.initials: FZ
authors.lastname: He
authors.forename: Zhi-Ying
authors.initials: ZY
authors.lastname: Luo
authors.forename: Jia-Gen
authors.initials: JG
authors.lastname: Wen
authors.forename: Lu-Yan
authors.initials: LY
authors.lastname: Wang
authors.forename: Ning-Ling
authors.initials: NL
authors.lastname: Sun
authors.forename: Gen-Fu
authors.initials: GF
authors.lastname: Tang
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Dong
authors.initials: D
authors.lastname: Guo
authors.forename: Zhao-Qian
authors.initials: ZQ
authors.lastname: Liu
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Zhou
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D044466:Asian People / Q000235:genetics; D003371:Cough / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D004656:Enalapril / Q000008:administration & dosage / Q000009:adverse effects*; D000075222:Essential Hypertension; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged
chemical_list: D000017:ABO Blood-Group System; D000806:Angiotensin-Converting Enzyme Inhibitors; D004656:Enalapril