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Genetic Associations of Angiotensin-Converting Enzyme with Primary Intracerebral Hemorrhage: A Meta-analysis

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  • Yuhao Sun
  • Ye Liu
  • Lora Talley Watts
  • Qingfang Sun
  • Zhihong Zhong
  • Guo-Yuan Yang
  • Liuguan Bian

Abstract

Background: A number of studies have reported an association of angiotensin-converting enzyme (ACE) gene polymorphism with primary intracerebral hemorrhage (PICH), however the reports have demonstrated inconclusive results. To clarify this conflict, we updated the previously performed meta-analysis by Peck et al., which revealed negative results, by investigating the ACE polymorphism and its correlation to PICH. Methods: PubMed and Embase databases (through Dec 2012) were searched for English articles on the relationship of the I/D polymorphism in ACE with PICH in humans. Summary odds ratios (ORs) were estimated and potential sources of heterogeneity and bias were explored. Results: A total of 805 PICH cases and 1641 control cases obtained from 8 case-control studies were included. The results suggest that in dominant genetic models, the ACE I/D polymorphic variant was associated with a 58% increase in susceptibility risk of PICH (OR = 1.58; 95% CI = 1.07–2.35 for DD vs. DI+II). However, in the subgroup analysis based on race, a significant increased risk was found in Asian DD homozygote carriers (OR = 1.76 and 95% CI = 1.16–2.66 for DD vs. DI+II), but not in Caucasian DD homozygote carriers (OR = 1.18, 95% CI = 0.36–3.88, P = 0.784 for DD vs. DI+II). The heterogeneity between studies was remarkable, and its major sources of heterogeneity were due to the year in which the study was published. No potential publication bias was observed in dominant genetic models. Conclusions: These data demonstrated evidence of a positive association between ACE I/D polymorphism with PICH, and suggested that the ACE gene is a PICH susceptible gene in Asian populations.

Suggested Citation

  • Yuhao Sun & Ye Liu & Lora Talley Watts & Qingfang Sun & Zhihong Zhong & Guo-Yuan Yang & Liuguan Bian, 2013. "Genetic Associations of Angiotensin-Converting Enzyme with Primary Intracerebral Hemorrhage: A Meta-analysis," PLOS ONE, Public Library of Science, vol. 8(6), pages 1-8, June.
    • Handle: RePEc:plo:pone00:0067402
    DOI: 10.1371/journal.pone.0067402
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    References listed on IDEAS

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    1. Zintzaras Elias, 2010. "The Generalized Odds Ratio as a Measure of Genetic Risk Effect in the Analysis and Meta-Analysis of Association Studies," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 9(1), pages 1-14, May.
    2. George Peck & Liam Smeeth & John Whittaker & Juan Pablo Casas & Aroon Hingorani & Pankaj Sharma, 2008. "The Genetics of Primary Haemorrhagic Stroke, Subarachnoid Haemorrhage and Ruptured Intracranial Aneurysms in Adults," PLOS ONE, Public Library of Science, vol. 3(11), pages 1-12, November.
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