Influence of a TNF-α Polymorphism on the Severity of Schistosomiasis Periportal Fibrosis in the Northeast of Brazil

The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) is an essential component in the host immune response to infection, and it has been reported to be an important mediator in severe periportal fibrosis (PPF). We hypothesized that the (-G308A) polymorphism of the TNF-α gene is associated with the severity of PPF and that these polymorphisms influence TNF-α expression. In this cross-sectional study, we genotyped these polymorphisms within the TNF-α gene in 256 Brazilian subjects infected with Schistosoma mansoni, with different patterns of PPF. The genotype (-308) AA was associated with a significant increase in the risk to advanced PPF (OR = 4.60; p = 0.009). In addition, median levels of TNF-α were higher in patients with moderate to advanced PPF, compared with mild fibrosis (20 and 17.3 pg/mL, respectively; p = 0.040). There was no association between average serum levels of TNF-α and (-G308A) TNF-α polymorphism. Our results suggest the (-308) AA genotype may be a risk factor for severity in advanced PPF, in this Brazilian population, and could potentially be used to predict the severity of advanced PPF in schistosomiasis.