Karina Trujillo-Murillo, Francisco J. Bosques-Padilla, Irma Calderón-Lozano, Sirelda Navar-Vizcarra, Elvira Garza-González, Alberto Niderhauser-García, Juan P. Flores-Gutiérrez, Pablo Zorrilla-Blanco, Ricardo Salinas-Garza, Ana M. Rivas-Estilla, Herminia G. Martínez-Rodríguez
Department of Biochemistry
and Molecular Medicine, School of Medicine, Autonomous University of
Nuevo Leon, Monterrey, NL, Mexico.
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-α) and Ala9Val manganese superoxide dismutase (MnSOD)
polymorphisms were associated with NASH in a case-control study of subjects from Northeast Mexico.
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/m2) and 100 healthy subjects (44 women and 56 men; mean age ± SD, 27.8 ± 10.8 years; BMI 23 ± 1.6
kg/m2). 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.
The frequency of G-238A TNF-α and 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 TNF-α polymorphism 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.
Our results suggest that G-238A TNF-α and 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.