AUTHOR=Pineda-Tenor Daniel , Gómez-Moreno Ana Zaida , Sánchez-Ruano Juan José , Artaza-Varasa Tomas , Virseda-Berdices Ana , Fernández-Rodríguez Amanda , Mendoza Pedro Molina , Jiménez-Sousa María Ángeles , Resino Salvador 

TITLE=MTHFR rs1801133 Polymorphism Is Associated With Liver Fibrosis Progression in Chronic Hepatitis C: A Retrospective Study

JOURNAL=Frontiers in Medicine

VOLUME=7

YEAR=2020

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2020.582666

DOI=10.3389/fmed.2020.582666

ISSN=2296-858X

ABSTRACT=<p><bold>Background:</bold> The <italic>MTHFR</italic> (methylenetetrahydrofolate reductase) rs1801133 polymorphism leads to higher circulating levels of homocysteine, which is related to several liver diseases. We aimed to evaluate the relationship between <italic>MTHFR</italic> rs1801133 polymorphism and liver fibrosis progression in HCV-infected patients.</p><p><bold>Methods:</bold> We conducted a preliminary retrospective cohort study in 208 non-cirrhotic HCV-infected patients. These subjects had at least two liver stiffness measurements (LSM), which were assessed using transient elastography, and no patient had cirrhosis at baseline. We analyzed the association between <italic>MTHFR</italic> rs1801133 and outcome variables using Generalized Linear Models.</p><p><bold>Results:</bold> HCV-infected patients were 47 years old, around 54% were males, a low frequency of high alcohol intake (13.5%) or prior use of intravenous drugs (10.1%). A total of 26 patients developed cirrhosis (LSM1 ≥ 12.5) during a median follow-up of 46.6 months. The presence of the rs1801133 C allele showed an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.90; 95%CI = 0.83–0.98; <italic>p</italic> = 0.020) and the cirrhosis progression (adjusted OR = 0.43; 95%CI = 0.19–0.95; <italic>p</italic> = 0.038). Besides, rs1801133 CT/CC genotype had an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.80; 95%CI = 0.68–0.95; <italic>p</italic> = 0.009) and the cirrhosis progression (adjusted OR= 0.21; 95%CI = 0.06–0.74; <italic>p</italic> = 0.015).</p><p><bold>Conclusions:</bold><italic>MTHFR</italic> rs1801133 C allele carriers presented a diminished risk of liver fibrosis progression and development of cirrhosis than rs1801133 T allele carriers. This statement supports the hypothesis that <italic>MTHFR</italic> rs1801133 polymorphism appears to play a crucial role in chronic hepatitis C immunopathogenesis.</p>