American Journal of Epidemiology Advance Access published online on June 1, 2006
American Journal of Epidemiology, doi:10.1093/aje/kwj179
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1 Faculty of Medicine, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Faculty of Medicine, Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Health Research Institute, Ottawa, Ontario, Canada
* To whom correspondence should be addressed. It has been suggested that a G-to-T transition in exon 2 of the factor XIIIA gene resulting in a substitution of leucine for valine at amino acid 34 (FXIII Val34Leu) protects against venous thromboembolism (VTE). However, the evidence to date is insufficient to incorporate testing for the FXIII Val34Leu variant into clinical practice. To determine whether genotypes with the FXIII Val34Leu variant are protective against VTE, the authors performed a meta-analysis of 12 studies with genotyping for the FXIII Val34Leu variant (3,165 objectively diagnosed VTE cases and 4,909 controls). When a random-effects model was used, the combined odds ratios for VTE were 0.63 (95% confidence interval: 0.46, 0.86) for the homozygotes of the FXIII Val34Leu variant, 0.89 (95% confidence interval: 0.80, 0.99) for the heterozygotes, and 0.85 (95% confidence interval: 0.77, 0.95) for the homozygotes and heterozygotes combined. Potential sources of heterogeneity and potential bias were explored. The meta-analysis provided evidence that the FXIII Val34Leu variant has a small, but significant protective effect against VTE. Since VTE is a complex disorder, this information, along with results of ongoing studies to identify additional genetic factors underlying VTE, will be crucial in developing accurate risk profiles to identify individuals at higher risk of VTE.
Received September 1, 2005
Accepted January 10, 2006
HUMAN GENOME EPIDEMIOLOGY (HUGE) REVIEW
Factor XIII Val34Leu Variant Is Protective against Venous Thromboembolism: A HuGE Review and Meta-Analysis
Philip S. Wells 1,
Josdalyne L. Anderson 2,
Dimitrios K. Scarvelis 3,
Steve P. Doucette 2,
and
France Gagnon 4 *
2 Ottawa Health Research Institute, Ottawa, Ontario, Canada
3 Faculty of Medicine, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
4 Faculty of Medicine, Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada; Ottawa Health Research Institute, Ottawa, Ontario, Canada
France Gagnon, E-mail: france.gagnon{at}utoronto.ca
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