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The genetics of venous thromboembolism A meta-analysis involving ~120,000 cases and 180,000 controls

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: http://dx.doi.org/10.1160/TH09-01-0013
Issue: 2009: 102/2 (Aug) pp. 183-420
Pages: 360-370

The genetics of venous thromboembolism A meta-analysis involving ~120,000 cases and 180,000 controls

- See additional contents by clicking on [Summary] -

Reya Gohil; George Peck; Pankaj Sharma
Imperial College Cerebrovascular Research Unit (ICCRU), Hammersmith Hospitals & Imperial College, London, UK

Keywords

Meta-analysis, pulmonary embolism, Deep vein thrombosis, Venous thrombosis, polymorphism, candidate genes, Genes

Summary

We conducted a systematic and comprehensive meta-analysis on all candidate genes to assess their genetic contribution to the aetiology of venous thromboembolism (VTE) (pulmonary embolism and deep venous thrombosis) in all ethnic groups. Electronic databases were searched until and including January 2008 for any candidate gene investigated in VTE. Odds ratios (OR) and 95% confidence intervals (CI) were determined for each gene disease association using fixed and random effect models. Our meta-analyses included ~126,525 cases and 184,068 controls derived from 173 case-control studies, which included 21 genes (28 polymorphisms). Statistically significant associations with VTE were identified for factor V G1691A (OR 9.45; 95% CI 6.72–13.30, p<0.0001), factor V A4070G (OR 1.24; 95% CI 1.02–1.52, p=0.03), prothrombin G20210A, (OR 3.17; 95% CI 2.19–3.46, p<0.00001), prothrombin G11991A, (OR 1.17; 95% CI 1.07–1.27, p=0.0007), PAI-1 4G/5G, (OR 1.62; 95% CI 1.22–2.16, p=0.0008), alpha-fibrinogen Thr312Ala (OR 1.37; 95% CI 1.14–1.64, p=0.0008), all in Caucasian populations. MTHFR/ C677T in Chinese/Thai populations (OR 1.57; 95% CI 1.23–2.00, p=0.0003), and ACE I/D in African American populations (OR 1.5; 95% CI 1.03–2.18, p=0.03) were found to be significantly associated with VTE. Factor XIII Val34Leu (OR 0.80; 95% CI 0.68–0.94, p=0.007) and β-fibrinogen 455 G/A (OR 0.84; 95% CI 0.72–0.97, p=0.02) both showed significantly protective effects. Our work supports a genetic aetiology to VTE disease and provides reliable risk estimates.

Online Supplementary Material

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