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The Genetics of Primary Haemorrhagic Stroke, Subarachnoid Haemorrhage and Ruptured Intracranial Aneurysms in Adults

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  • George Peck
  • Liam Smeeth
  • John Whittaker
  • Juan Pablo Casas
  • Aroon Hingorani
  • Pankaj Sharma

Abstract

Background: The genetic basis of haemorrhagic stroke has proved difficult to unravel, partly hampered by the small numbers of subjects in any single study. A meta-analysis of all candidate gene association studies of haemorrhagic stroke (including ruptured subarachnoid haemorrhage and amyloid angiopathy-related haemorrhage) was performed, allowing more reliable estimates of risk. Methods: A systematic review and meta-analysis of all genetic studies in haemorrhagic stroke was conducted. Electronic databases were searched until and including March 2007 for any candidate gene in haemorrhagic stroke. Odds ratio (OR) and 95% confidence intervals (CI) were determined for each gene disease association using fixed and random effect models. Results: Our meta-analyses included 6,359 cases and 13,805 controls derived from 55 case-control studies, which included 12 genes (13 polymorphisms). Statistically significant associations with haemorrhagic stroke were identified for those homozygous for the ACE/I allele (OR, 1.48; 95% CI, 1.20–1.83; p = 0.0003) and for the 5G allele in the SERPINE1 4G/5G polymorphism (OR, 1.42; 95% CI, 1.03–1.96; p = 0.03). In addition, both &b.epsi;2 and &b.epsi;4 alleles of APOE were significantly associated with lobar haemorrhage (OR, 1.81; 95% CI, 1.26–2.62; p = 0.002 and OR, 1.49; 95% 1.08–2.05; p = 0.01 respectively). Furthermore, a significant protective association against haemorrhagic stroke was found for the factor V Leiden mutation (OR, 0.30; 95% CI, 0.10–0.87; p = 0.03). Conclusion: Our data suggests a genetic contribution to some types of haemorrhagic stroke, with no overall responsible single gene but rather supporting a polygenic aetiology . However, the evidence base is smaller compared to ischaemic stroke. Importantly, for several alleles previously found to be associated with protection from ischaemic stroke, there was a trend towards an increased risk of haemorrhagic stroke.

Suggested Citation

  • 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.
    • Handle: RePEc:plo:pone00:0003691
    DOI: 10.1371/journal.pone.0003691
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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.
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    Cited by:

    1. 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.
    2. 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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