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Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Susceptibility to Osteoarthritis of the Knee: A Case-Control Study and Meta-Analysis

Author

Listed:
  • Chin Lin
  • Hsiang-Cheng Chen
  • Wen-Hui Fang
  • Chih-Chien Wang
  • Yi-Jen Peng
  • Herng-Sheng Lee
  • Hung Chang
  • Chi-Ming Chu
  • Guo-Shu Huang
  • Wei-Teing Chen
  • Yu-Jui Tsai
  • Hong-Ling Lin
  • Fu-Huang Lin
  • Sui-Lung Su

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.

Suggested Citation

  • Chin Lin & Hsiang-Cheng Chen & Wen-Hui Fang & Chih-Chien Wang & Yi-Jen Peng & Herng-Sheng Lee & Hung Chang & Chi-Ming Chu & Guo-Shu Huang & Wei-Teing Chen & Yu-Jui Tsai & Hong-Ling Lin & Fu-Huang Lin , 2016. "Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Susceptibility to Osteoarthritis of the Knee: A Case-Control Study and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 11(9), pages 1-18, September.
    • Handle: RePEc:plo:pone00:0161754
    DOI: 10.1371/journal.pone.0161754
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    References listed on IDEAS

    as
    1. Chin Lin & Chi-Ming Chu & John Lin & Hsin-Yi Yang & Sui-Lung Su, 2015. "Gene-Gene and Gene-Environment Interactions in Meta-Analysis of Genetic Association Studies," PLOS ONE, Public Library of Science, vol. 10(4), pages 1-13, April.
    2. Zang, Yong & Fung, Wing Kam & Zheng, Gang, 2010. "Simple Algorithms to Calculate Asymptotic Null Distributions of Robust Tests in Case-Control Genetic Association Studies in R," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 33(i08).
    3. Viechtbauer, Wolfgang, 2010. "Conducting Meta-Analyses in R with the metafor Package," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 36(i03).
    4. Chin Lin & Chi-Ming Chu & Sui-Lung Su, 2016. "Epistasis Test in Meta-Analysis: A Multi-Parameter Markov Chain Monte Carlo Model for Consistency of Evidence," PLOS ONE, Public Library of Science, vol. 11(4), pages 1-17, April.
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