title: Genes associated with adult cerebral venous thrombosis.
abstract: OBJECTIVE
  Quantitative predictions of the risk of cerebral venous thrombosis (CVT) conferred by certain genotypes have yet to be reliably established. We conducted a comprehensive meta-analysis of all candidate genes studied to assess their genetic contribution to the etiology of CVT. We compared our findings against equivalent analyses for pediatric CVT and adult ischemic stroke.
  
  
  METHODS
  Databases were searched to August 2010 for all genes investigated in adult CVT, and odds ratios (ORs) for each gene-disease association were calculated. A mendelian randomization strategy was also undertaken to determine whether a causal relation to one gene could be ascertained.
  
  
  RESULTS
  We identified 26 case-control studies investigating 6 polymorphisms in 6 genes and included 1183 CVT cases and 5189 controls. Statistically significant associations with CVT were found for factor V Leiden/G1691A (OR=2.40; 95% CI, 1.75 to 3.30; P<0.00001) and prothrombin/G20210A (OR=5.48; 95% CI, 3.88 to 7.74; P<0.00001). After iterative analysis controlling for interstudy heterogeneity, methylene tetrahydrofolate reductase/C677T was also found to be significantly associated (OR=2.30; 95% CI, 1.20 to 4.42; P=0.02). Variants in the remaining 3 genes (Janus kinase-2, plasminogen activator inhibitor-1, and protein Z) were not significantly associated. Pooled ORs for CVT risk in adults for factor V Leiden and prothrombin were significantly greater when compared against childhood CVT and adult arterial ischemic stroke. A causal relation with methylene tetrahydrofolate reductase may exist.
  
  
  CONCLUSIONS
  CVT has a genetic basis. Genes involved in the clotting cascade provide a greater level of thrombosis risk in the cerebral venous circulation compared with its arterial circulation, and a greater level of risk exists for adults compared with children.
authors.affiliation: Imperial College Cerebrovascular Research Unit, Department of Clinical Neuroscience, Imperial College London, Fulham Palace Road, London W6 8RF, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Marjot
authors.forename: Sunaina
authors.initials: S
authors.lastname: Yadav
authors.forename: Nazeeha
authors.initials: N
authors.lastname: Hasan
authors.forename: Paul
authors.initials: P
authors.lastname: Bentley
authors.forename: Pankaj
authors.initials: P
authors.lastname: Sharma
mesh_terms: D000328:Adult; D000367:Age Factors; D001777:Blood Coagulation / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D005165:Factor V / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D020767:Intracranial Thrombosis / Q000235:genetics* / Q000378:metabolism; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D016017:Odds Ratio; D011516:Prothrombin / Q000235:genetics; D016032:Randomized Controlled Trials as Topic / Q000639:trends; D020246:Venous Thrombosis / Q000235:genetics* / Q000378:metabolism
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D042965:Methylenetetrahydrofolate Reductase (NADPH2)