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The genetics of Cerebral Sinovenous Thrombosis; a meta-analysis of > 2000 CSVT patients and > 9000 controls
Marjot T1, Yadav S2, Sharma P2
1Imperial College School of Medicine, UK, 2Imperial College Cerebrovascular Research Unit (ICCRU), London, UK
Introduction: We conducted a systematic review and comprehensive meta-analysis of all candidate genes to assess their genetic contribution to the aetiology of cerebral sinovenous thrombosis (CSVT). Genetic thrombophilias have been predicted to underpin around 22% of CSVT cases but quantitative predictions of risk conferred by certain genotypes have yet to be conclusively established.
Method: Electronic databases and library journals were searched up until the beginning of April 2010 for any genes investigated in CSVT, in either adult or paediatric populations. Odds Ratios (OR) and 95% Confidence Intervals (CI) for each gene-disease association were calculated using fixed and random effects model.
Results: Our meta-analysis incorporated 55 case-control studies, investigating seven polymorphisms in seven genes and included >2000 CSVT patients and > 9000 controls. Statistically significant associations were found for Factor V G1691A (OR; adults; 2.56 (1.92–3.42), children; 2.75 (1.75–4.33)), Prothrombin G20210A (OR; adults; 6.37 (4.67–8.69), children; 2.58 (1.19–5.61)) and after controlling for heterogeneity, MTHFR C677T (OR; adults; 1.60 (95% CI, 1.07–2.38)). Using the principles of Mendelian randomisation, the OR for MTHFR C677T was compared to the effect size predicted from independent biochemical data, in this case homocysteine. This allowed us to hypothesise a causal relationship between the MTHFR polymorphism and CSVT.
Conclusion: Our work supports a possible genetic aetiology to CSVT, provides reliable risk estimates and allows accurate comparison with genetic risk in other vascular conditions.
