G308A polymorphism of TNF-alpha gene is associated with insulin resistance and histological changes in non alcoholic fatty liver disease patients.

Some studies have pointed to a role of TNF-alpha in pathogenesis of non alcoholic fatty liver disease (NAFLD). The aim of our study was to investigate the influence of G308A polymorphism TNF alpha gene on the histological changes, insulin resistance and TNF-alpha levels in overweight patients. A population of 66 patients with NAFLD was recruited in a cross sectional study. A biochemical analysis of serum was measured. Genotype of TNF alpha gene G308A was studied. Fifteen patients (22.7%) had the genotype G308A (mutant type group) and 51 patients (77.3%) G308G (wild type group). Patients with mutant type group presented more moderate-severe portal inflammation (86.7%) in liver biopsy compared to patient with wild genotype (19.7%). Mutant type group had more moderate-severe fibrosis (73.3%) than wild type group (51.3%). The multivariate analysis adjusted by age, sex, BMI and genotype with the dependent variable (fibrosis) showed that HOMA remained in the model, with an increase of the probability to develop fibrosis of 1.78 (CI95%:1.06-3.2) and develop moderate-severe inflammation of 1.45 (CI95%:1.02-2.1) with each increase of one unit on HOMA levels. In conclusion, Patients with mutant genotype have more frequently moderate-severe portal inflammation and fibrosis than wild type genotype.