American Journal of Epidemiology Advance Access originally published online on June 1, 2006
American Journal of Epidemiology 2006 164(2):101-109; doi:10.1093/aje/kwj179
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Human Genome Epidemiology (HuGE) Review |
Factor XIII Val34Leu Variant Is Protective against Venous Thromboembolism: A HuGE Review and Meta-Analysis
1 Faculty of Medicine, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada
2 Faculty of Medicine, Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada
3 Ottawa Health Research Institute, Ottawa, Ontario, Canada
Reprint requests to Dr. France Gagnon, Department of Public Health Sciences, Faculty of Medicine, University of Toronto, Health Sciences Building, 155 College Street, Toronto, Ontario M5T 3M7, Canada (e-mail: france.gagnon{at}utoronto.ca).
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.
epidemiology; factor XIII; FXIII Val34Leu; genetics; leucine; meta-analysis; valine; venous thrombosis
Abbreviations: CI, confidence interval; FXIII, factor XIII; FXIIIA, factor XIII A subunit; FXIII Val34Leu, factor XIII Valine34Leucine variant; Leu, leucine; Val, valine; VTE, venous thromboembolism
Editor's note: This paper is also available on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/).
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