A Comprehensive Study of Tumor Necrosis Factor-Alpha Genetic Polymorphisms, its Expression in Skin and Relation to Histopathological Features in Psoriasis

Background : Tumor necrosis factor-alpha (TNF alpha) is an important inflammatory mediator in psoriasis and several genetic polymorphisms of this cytokine have been reported. Majority of studies have focused on the increased G- A polymorphism at the -308 position in psoriasis. There has been no comprehensive study evaluating the genetic polymorphisms, TNF alpha expression in the skin and histopathology. We are undertaking this study to outline TNF alpha genetic polymorphisms, its skin expression and histopathological correlation to help determine its role at the genetic and protein level. Materials and Methods : 112 patients of psoriasis and 243 healthy controls were included in this prospective study. 5 ml of peripheral blood was collected to study the TNF alpha genetic polymorphisms by polymerase chain reaction and restriction fragment length polymorphism analysis. Histopathological analysis of biopsies from the 112 patients were done using visual analogue scale and correlated with the findings. 61 of these cases were analyzed for TNF alpha expression by immunohistochemistry. The results of study were statistically analyzed using SPSS 13.0 statistical package program. Results : A strong association of TNF alpha -308 G/A polymorphism in psoriasis cases was detected. The A allele of the TNF alpha -308 G/A polymorphism occurs rarely in the Indian population, however there is an over representation of this allele in psoriatic patients. There was no association seen between TNF alpha genotype and histopathological severity of psoriasis. Conclusion : The study emphasized the central role of TNF alpha in the pathogenesis of psoriasis. TNFa genotyping may be helpful in identifying subjects in whom anti-TNF alpha therapeutic strategies may be tried.