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

Abstract

Background: The MTHFR (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 MTHFR rs1801133 polymorphism and liver fibrosis progression in HCV-infected patients. Methods: 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 MTHFR rs1801133 and outcome variables using Generalized Linear Models. Results: 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; p = 0.020) and the cirrhosis progression (adjusted OR = 0.43; 95%CI = 0.19–0.95; p = 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; p = 0.009) and the cirrhosis progression (adjusted OR= 0.21; 95%CI = 0.06–0.74; p = 0.015). Conclusions: MTHFR 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 MTHFR rs1801133 polymorphism appears to play a crucial role in chronic hepatitis C immunopathogenesis.

NOTCH3 rs1043996 Polymorphism Is Associated with the Occurrence of Alcoholic Liver Cirrhosis Independently of PNPLA3 and TM6SF2 Polymorphisms

“…This includes two recent meta-analyses, one of which confirmed the association, while the other rejected it, with the exception of the Asian subpopulation [ 9 , 11 , 37 ]. Recently, Pineda-Tenor et al [ 38 ] reported that MTHFR rs1801133 polymorphism is associated with the progression of liver fibrosis in chronic hepatitis C. However, we found no association between the MTHFR polymorphism and susceptibility to ALC or HCC.…”

TRPM5 rs886277 Polymorphism Predicts Hepatic Fibrosis Progression in Non-Cirrhotic HCV-Infected Patients

“…We found that patients carrying rs886277 C allele and CC genotype had an increased risk of liver fibrosis progression and cirrhosis development. The association found between TRPM5 rs886277 polymorphism and liver fibrosis and cirrhosis was independent of the effect of other SNPs, since logistic regression models were adjusted by the most relevant covariables, including five SNPs previously reported in this cohort ( MERTK rs4374383 [ 37 ], PNPLA3 rs738409 [ 38 ], IL7RA rs6897932 [ 35 ], MTHFR rs1801133 [ 39 ], and DARC rs12075 [ 30 ]). These five SNPs were related to liver fibrosis progression and development of cirrhosis [ 30 , 35 , 37 , 38 , 39 ].…”

“…A GLM with binomial distribution was used to analyze cirrhosis progression, which provides the odds ratio (OR). GLM tests were adjusted by the most relevant covariables selected by a stepwise algorithm ( p -value < 0.20 at each step) from the following list of variables: age, gender, time since HCV diagnosis, diabetes, injection drug use, high alcohol intake, time of follow-up, baseline LSM, HCV treatment (before and after starting the study among non-responder patients), HCV genotype, and other significant SNPs previously analyzed in this cohort (MERTK rs4374383 [ 37 ], PNPLA3 rs738409 [ 38 ], IL7RA rs6897932 [ 35 ], MTHFR rs1801133 [ 39 ], and DARC rs12075 [ 30 ]).…”