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Methylenetetrahydrofolate reductase C677T polymorphism and liver fibrosis progression in patients with recurrent hepatitis C
Authors:Pierluigi Toniutto  Carlo Fabris  Edmondo Falleti  Annarosa Cussigh  Elisabetta Fontanini  Davide Bitetto  Ezio Fornasiere  Rosalba Minisini  Tullia De Feo  Francesca Marangoni  Mario Pirisi
Institution:1. Department of Pathology and Medicine Experimental and Clinical, Medical Liver Transplant Unit, University of Udine, Udine, Italy;2. Department of Clinical and Experimental Medicine, University of Eastern Piedmont ‘Amedeo Avogadro', Novara, Italy;3. Interdisciplinary Research Center on Autoimmune Diseases (IRCAD), University of Eastern Piedmont ‘Amedeo Avogadro’, Novara, Italy;4. North Italy Transplant Program – IRCCS Fondazione Ospedale Maggiore, Milano, Italy
Abstract:Background/Aims: Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, being a putative steatogenic factor, may promote liver fibrosis progression in patients with chronic hepatitis C. This study aimed to verify the role of recipient MTHFR polymorphism in favouring graft fibrosis progression in patients with recurrent HCV after orthotopic liver transplantation (OLT). Methods: We studied 63 such patients, followed for >1 year. MTHFR allelic variants were determined by a polymerase chain reaction/restriction fragment length polymorphism method. Results: Recipients carrying the TT genotype had more frequently, 1‐year post‐OLT, homocysteine serum levels >23 μmol/L (P<0.05), serum triglycerides >180 mg/dL (P<0.02) and de novo diabetes mellitus (P<0.05) but not a higher frequency of graft steatosis. Time‐to‐event analysis in reaching an Ishak staging score >2 was performed by stratifying the recipients as follows: (a) patients with donor age ≤45 years, (b) patients with donor age >45 and C/* genotype, and (c) patients with donor age >45 years and TT genotype. A significant linear trend was observed, with increasing frequencies as follows: (a) 8/37, (b) 10/19 and (c) 6/7 (P=0.0005). Conclusion: The MTHFR C677T polymorphism may play a role in influencing liver fibrosis progression in patients with recurrent hepatitis C, in conjunction with donor age, but not via steatosis promotion.
Keywords:hepatitis C  liver fibrosis  liver transplantation  MTHFR gene
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