title: Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Susceptibility to Osteoarthritis of the Knee: A Case-Control Study and Meta-Analysis.
abstract: BACKGROUND
  Studies of angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and the risks of knee osteoarthritis (OA) have yielded conflicting results.
  
  
  OBJECTIVE
  To determine the association between ACE I/D and knee OA, we conducted a combined case-control study and meta-analysis.
  
  
  METHODS
  For the case-control study, 447 knee OA cases and 423 healthy controls were recruited between March 2010 and July 2011. Knee OA cases were defined using the Kellgren-Lawrence grading system, and the ACE I/D genotype was determined using a standard polymerase chain reaction. The association between ACE I/D and knee OA was detected using allele, genotype, dominant, and recessive models. For the meta-analysis, PubMed and Embase databases were systematically searched for prospective observational studies published up until August 2015. Studies of ACE I/D and knee OA with sufficient data were selected. Pooled results were expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for the D versus I allele with regard to knee OA risk.
  
  
  RESULTS
  We found no significant association between the D allele and knee OA [OR: 1.09 (95% CI: 0.76-1.89)] in the present case-control study, and the results of other genetic models were also nonsignificant. Five current studies were included, and there were a total of six study populations after including our case-control study (1165 cases and 1029 controls). In the meta-analysis, the allele model also yielded nonsignificant results [OR: 1.37 (95% CI: 0.95-1.99)] and a high heterogeneity (I2: 87.2%).
  
  
  CONCLUSIONS
  The association between ACE I/D and knee OA tended to yield negative results. High heterogeneity suggests a complex, multifactorial mechanism, and an epistasis analysis of ACE I/D and knee OA should therefore be conducted.
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Chin
authors.initials: C
authors.lastname: Lin
authors.affiliation: Division of Rheumatology/Immunology/Allergy, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Hsiang-Cheng
authors.initials: HC
authors.lastname: Chen
authors.affiliation: Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Fang
authors.affiliation: Department of Orthopedics, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Chih-Chien
authors.initials: CC
authors.lastname: Wang
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Peng
authors.affiliation: Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC.
authors.forename: Herng-Sheng
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan‏, ROC.|Division of Thoracic Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Hung
authors.initials: H
authors.lastname: Chang
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: Department of Radiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Guo-Shu
authors.initials: GS
authors.lastname: Huang
authors.affiliation: Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan, ROC.|Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Wei-Teing
authors.initials: WT
authors.lastname: Chen
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Yu-Jui
authors.initials: YJ
authors.lastname: Tsai
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Hong-Ling
authors.initials: HL
authors.lastname: Lin
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Fu-Huang
authors.initials: FH
authors.lastname: Lin
authors.affiliation: School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Sui-Lung
authors.initials: SL
authors.lastname: Su