Portal vein thrombosis in Egyptian patients with liver cirrhosis: Role of methylenetetrahydrofolate reductase C677T gene mutation

Aim: The pathogenesis of non-malignant portal vein thrombosis (PVT) in cirrhotic patients is not clearly defined. This case-control study aimed to investigate the role of methylenetetrahydrofolate reductase (MTHFR) C677T gene mutation in the pathogenesis of PVT in Egyptian cirrhotic patients. Methods: Plasma homocysteine was measured and MTHFR C677T gene mutation was detected in 76 cirrhotic patients (21 with PVT, 55 without PVT) and 20 healthy controls. Results: The frequency of CC genotype (wide type) in cirrhotic patients with PVT was lower than controls and cirrhotics without PVT. However, the frequency of TT genotype (homozygous mutation) was elevated in cirrhotic patients with PVT as compared to controls and those without PVT. Cirrhotic patients with PVT had significantly higher homocysteine than those without PVT. Cirrhotic patients with TT genotype are at a significant risk for PVT (odds ratio = 7.7, 95% confidence interval, 1.50-42.81) when compared with CC genotype. Moreover, subjects carrying TT genotype had a higher homocysteine than those carrying CC genotype. Conclusions: The TT genotype of MTHFR is associated with an increased risk of PVT in Egyptian cirrhotic patients. Hyperhomocysteinemia could be considered as a relatively new risk factor for PVT in cirrhotic patients and plasma homocysteine should be investigated particularly in patients with PVT of unexplained etiology. The important clinical implication is that the readily available therapy of folate, vitamin B6 and B12 supplementation may reduce homocysteine and prevent further thrombotic complications in cirrhotic patients carrying the TT genotype.