BACKGROUND AND PURPOSE: 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.
BACKGROUND AND PURPOSE: 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: Gie Ken-Dror; Ioana Cotlarciuc; Ida Martinelli; Elvira Grandone; Sini Hiltunen; Erik Lindgren; Maurizio Margaglione; Veronique Le Cam Duchez; Aude Bagan Triquenot; Marialuisa Zedde; Michelangelo Mancuso; Ynte M Ruigrok; Thomas Marjot; Brad Worrall; Jennifer J Majersik; Tiina M Metso; Jukka Putaala; Elena Haapaniemi; Susanna M Zuurbier; Matthijs C Brouwer; Serena M Passamonti; Maria Abbattista; Paolo Bucciarelli; Braxton D Mitchell; Steven J Kittner; Robin Lemmens; Christina Jern; Emanuela Pappalardo; Paolo Costa; Marina Colombi; Diana Aguiar de Sousa; Sofia Rodrigues; Patrícia Canhão; Aleksander Tkach; Rosa Santacroce; Giovanni Favuzzi; Antonio Arauz; Donatella Colaizzo; Kostas Spengos; Amanda Hodge; Reina Ditta; Alessandro Pezzini; Stephanie Debette; Jonathan M Coutinho; Vincent Thijs; Katarina Jood; Guillaume Pare; Turgut Tatlisumak; José M Ferro; Pankaj Sharma Journal: Ann Neurol Date: 2021-09-29 Impact factor: 10.422