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

Abstract

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 TNF-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-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. Conclusions: Our results suggest that G-238A TNF-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.

PNPLA3 and TNF-<i>α</i> G238A Genetic Polymorphisms in Egyptian Patients with Different Grades of Severity of NAFLD

“…Our results agree with the results of Trujillo-Murillo et al, who reported that the frequency of the -238 TNF-α polymorphism was significantly higher in NASH patients than in controls (29% vs 12%; p value = 0.0047) [47]. The study by Valenti et al also found a higher frequency of -238 polymorphisms but not of the -308 TNF polymorphisms in Italian patients with NAFLD [43].…”

The genetic interactions between non-alcoholic fatty liver disease and cardiovascular diseases

“…Candidate gene studies have identified several polymorphisms in the TNF-α gene promotor (Qidwai and Khan, 2011). The higher prevalence of the TNF-α/-238 promotor polymorphism in NAFLD or NASH patients, compared to controls, are reported in the Italian (Valenti et al, 2002), Mexican and Chinese (Hu et al, 2009;Zhou et al, 2010;Trujillo-Murillo et al, 2011) cohorts. In the Japanese, two other polymorphisms have instead been identified, -1031C and -863A (Tokushige et al, 2007).…”

Association of tumor necrosis factor‐α gene promoter polymorphism at sites ‐308 and ‐238 with non‐alcoholic fatty liver disease: A meta‐analysis

“…Valenti L et al 17 Huang J et al 18 Tokushige K et al 19 Wong VW et al 20 Hu ZW et al 21 Zhou YJ et al 23 Trujillo-Murillo K et al 24 Total (95% CI) Total events Heterogeneity: Chi² = 9.22, df = 6 (P = 0.16); I² = 35% Test for overall effect: Z = 5.33 (P < 0.00001) ated with insulin resistance and increased body mass index (BMI) in NAFLD patients, contributing to the pathogenesis of NAFLD. Chinese researchers 21,23 also demonstrated an association between -238 A allele (TNFA) polymorphism and increasing serum TNF-a in Chinese patients with NAFLD.…”