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Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Contributes to Ischemic Stroke Risk: A Meta-Analysis of 50 Case-Control Studies

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  • Zhizhong Zhang
  • Gelin Xu
  • Dezhi Liu
  • Xinying Fan
  • Wusheng Zhu
  • Xinfeng Liu

Abstract

Background: Many studies have investigated the association between the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and risk of ischemic stroke. However, the evidence is inadequate to draw robust conclusions because most studies were generally small and conducted in heterogeneous populations. To shed light on these inconclusive findings, we conducted a large meta-analysis of studies relating the ACE I/D polymorphism to the risk of ischemic stroke. Methods: Relevant studies were identified by searching PubMed and Embase through February 2012 and by reviewing the references of retrieved articles. We included studies that reported odds ratio (OR) with 95% confidence interval (CI) for the association between this polymorphism and ischemic stroke risk. Results: Fifty independent publications, with 10 070 stroke cases and 22 103 controls, were included. The results indicated that the DD homozygote carriers had a 37% higher risk of ischemic stroke when compared with the homozygotes II and heterozygote ID [odds ratio (OR) = 1.37, 95% confidence interval (CI): 1.22–1.53]. Subgroup analyses indicated that this higher risk was more pronounced among Asians, hospital-based studies, and small vessel disease (SVD). Potential publication bias may exist, but correction for this bias using a formal statistical method did not materially alter the combined risk estimate. Conclusion: The results of our meta-analysis indicate that the D allele of ACE I/D polymorphism is a low-penetrance susceptibility marker of ischemic stroke.

Suggested Citation

  • Zhizhong Zhang & Gelin Xu & Dezhi Liu & Xinying Fan & Wusheng Zhu & Xinfeng Liu, 2012. "Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Contributes to Ischemic Stroke Risk: A Meta-Analysis of 50 Case-Control Studies," PLOS ONE, Public Library of Science, vol. 7(10), pages 1-9, October.
    • Handle: RePEc:plo:pone00:0046495
    DOI: 10.1371/journal.pone.0046495
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    References listed on IDEAS

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    1. Roshan Ariyaratnam & Juan P Casas & John Whittaker & Liam Smeeth & Aroon D Hingorani & Pankaj Sharma, 2007. "Genetics of Ischaemic Stroke among Persons of Non-European Descent: A Meta-Analysis of Eight Genes Involving ∼ 32,500 Individuals," PLOS Medicine, Public Library of Science, vol. 4(4), pages 1-9, April.
    2. Sue Duval & Richard Tweedie, 2000. "Trim and Fill: A Simple Funnel-Plot–Based Method of Testing and Adjusting for Publication Bias in Meta-Analysis," Biometrics, The International Biometric Society, vol. 56(2), pages 455-463, June.
    3. Paul Bentley & George Peck & Liam Smeeth & John Whittaker & Pankaj Sharma, 2010. "Causal Relationship of Susceptibility Genes to Ischemic Stroke: Comparison to Ischemic Heart Disease and Biochemical Determinants," PLOS ONE, Public Library of Science, vol. 5(2), pages 1-15, February.
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