title: Impact of interaction of cigarette smoking with angiotensin-converting enzyme polymorphisms on end-stage renal disease risk in a Han Chinese population.
abstract: BACKGROUND
  Several polymorphisms in the angiotensin-converting enzyme (ACE) and ACE2 genes are associated with the development of end-stage renal disease (ESRD). Certain genetic polymorphisms may modify the deleterious effects of environmental factors such as cigarette smoking and may also modify the inherited risk. We investigated the association of six ACE and ACE2 polymorphisms with ESRD to determine whether a relationship exists between gene-smoking interactions and ESRD.
  
  
  METHODS
  We performed a case-control association study and genotyped 683 ESRD patients and 653 healthy controls. All subjects were genotyped for ACE (I/D, G2350A and A-240T) and ACE2 (G8790A, A1075G and G16854C) gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.
  
  
  RESULTS
  Significant associations were observed between ACE I/D and G2350A polymorphisms and ESRD. There was no difference in ACE2 genotype distribution between ESRD patients and healthy controls. Haplotype analysis showed that DAA and DAT haplotypes were risk factors for ESRD. Moreover, a gene-environment interaction was observed between ACE I/D polymorphism and cigarette smoking.
  
  
  CONCLUSIONS
  ACE I/D and ACE G2350A polymorphisms were associated with the development of ESRD. The interaction between ACE I/D polymorphism and smoking is also associated with an enhanced risk of ESRD.
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Yang
authors.affiliation: Division of Nephrology, Department of Medicine, Cardinal Tien Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, ROC.
authors.forename: Kuo-Cheng
authors.initials: KC
authors.lastname: Lu
authors.affiliation: Department of Family and Community Medicine, Tri-Service General Hospital, Taipei, Taiwan, ROC.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Fang
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Herng-Sheng
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Chia-Chao
authors.initials: CC
authors.lastname: Wu
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC Division of Nephrology, Department of Medicine, Shuang Ho Hospital, Graduate Institute of Clinical Medicine, Taipei Medical University, New Taipei City, Taiwan, ROC.
authors.forename: Yuh-Feng
authors.initials: YF
authors.lastname: Lin
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Sen-Yeong
authors.initials: SY
authors.lastname: Kao
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Ching-Huang
authors.initials: CH
authors.lastname: Lai
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Chu
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC a131419@gmail.com.
authors.forename: Sui-Lung
authors.initials: SL
authors.lastname: Su
mesh_terms: D000367:Age Factors; D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D044466:Asian People / Q000706:statistics & numerical data; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D004298:Dopamine / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects* / Q000453:epidemiology*
chemical_list: C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; D004298:Dopamine
keywords: End-stage renal disease (ESRD); angiotensin-converting enzyme (ACE); angiotensin-converting enzyme 2 (ACE2); cigarette smoking; single nucleotide polymorphism (SNP)