Homozygous Mthfr C677t Carriers Develop Idiopathic Portal Vein Thrombosis Twenty Years Earlier Than Wild Type

Abstract Objective: To compare age at occlusion and plasma homocysteine (HC) in patients with idiopathic portal vein thrombosis (PVT) genotyped for methylene tetrahydrofolate reductase (MTHFR) rs1801133 (C®T667 transition), to identify which clinical or laboratory variables influenced age at first PVT, including the prothrombin rs1799963 PT (G®A transition at position 20210) (PT) mutation. Methods: Retrospective cross-sectional cohort survey on 17 MTHFR TT, 45 MTHFR TC and 24 MTHFR CC participants with idiopathic PVT who contributed age, sex, age at PVT, smoking status, plasma HC and natural anticoagulant concentrations. Results: Age at PVT was lower in MTHFR TT than MTHFR TC and CC (31±8 vs. 46±16 vs. 52±14 years, respectively, p=0.001); median (IQR) plasma HC was higher in MTHFR TT than in the other groups [17 (12.6,25.0) vs. 10 (7.4,13.1) vs. 11.9 (8.1,5.8) μmol/l, respectively, p=0.002)]. MTHFR TT and protein C independently predicted age at PVT (p<0.0001 and p=0.04 respectively); MTHFR TT independently predicted plasma HC (p=0.05). Smoking and sex predicted cavernoma (p=0.002 and p=0.02 respectively). Compound MTHFR TT with PT GA had no lowering effect on age at first VTE compared to MTHFR TT alone (37±7 vs. 30±8 years). Conclusions: MTHFR TT anticipates age at PVT by an average of 20 years compared to other MTHFR genotypes. PT GA had no age lowering effect combined with MTHFR TT. Smoking predicts cavernoma formation, suggesting that smoking may associate with recurrent subclinical PVT before the symptomatic presentation.