Association of Tumor Necrosis Factor and Manganese Superoxide Dismutase Polymorphisms in Patients with Non-Alcoholic Steatohepatitis from Northeast Mexico

Background and Aims: Environmental and genetic factors play a role in the pathogenesis and natural history of non-alcoholic steatohepatitis (NASH). The aim of this study was to determine if the G-238A (allele TNFA) and G-308A (allele TNF2) tumor necrosis factor-alpha (TNF) and Ala9Val manganese superoxide dismutase (MnSOD) polymorphisms were associated with NASH in a case-control study of subjects from Northeast Mexico. Methods: We analyzed DNA samples from 68 patients with NASH (50 women and 18 men; mean age ± SD, 33.9 ± 10.8 years; BMI 43.9 ± 7.2 kg/m 2 ) and 100 healthy subjects (44 women and 56 men; mean age ± SD, 27.8 ± 10.8 years; BMI 23 ± 1.6 kg/m 2 ). The diagnosis was based on liver biopsy reviewed by two pathologists blinded to clinical data. The polymorphisms were evaluated using the polymerase chain reaction-restriction fragment length polymorphism method. Results: The frequency of G-238A TNFand Ala9Val MnSOD polymorphisms in NASH patients was significantly higher in comparison with control subjects (OR = 3.06, 95% CI 1.29-7.33, p = 0.0047 and OR = 6.28, 95% CI 2.95-13.55, p = 0.001, respectively). In contrast, the G-308A TNFpolymorphism did not show a statistical difference between either group (OR = 1.04, 95% CI 0.45-2.38, p = NS). Analyzed populations were in Hardy-Weinberg equilibrium. Conclusions: Our results suggest that G-238A TNFand Ala9Val MnSOD polymorphisms, which are molecules involved in inflammation and cellular oxidative stress, could be associated with NASH. These data may contribute to understanding the genetic susceptibility to NASH.