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Genetic polymorphisms in  TNFB  are involved in the regulation of its expression and are found to be associated with various autoimmune diseases. The aim of the present study was to determine whether  TNFB  +252A/G (rs909253) and exon 3 C/A (rs1041981) polymorphisms are associated with vitiligo susceptibility, and expression of  TNFB  and  ICAM1  affects the disease onset and progression. We have earlier reported the role of  TNFA  in autoimmune pathogenesis of vitiligo, and we now show the involvement of  TNFB  in vitiligo pathogenesis. The two polymorphisms investigated in the  TNFB  were in strong linkage disequilibrium and significantly associated with vitiligo.  TNFB  and  ICAM1  transcripts were significantly increased in patients compared to controls. Active vitiligo patients showed significant increase in  TNFB  transcripts compared to stable vitiligo. The genotype-phenotype analysis revealed that  TNFB  expression levels were higher in patients with GG and AA genotypes as compared to controls. Patients with the early age of onset and female patients showed higher  TNFB  and  ICAM1  expression. Overall, our findings suggest that the increased  TNFB  transcript levels in vitiligo patients could result, at least in part, from variations at the genetic level which in turn leads to increased  ICAM1  expression. For the first time, we show that  TNFB  +252A/G and exon 3 C/A polymorphisms are associated with vitiligo susceptibility and influence the  TNFB  and  ICAM1  expression. Moreover, the study also emphasizes influence of  TNFB  and  ICAM1  on the disease progression, onset and gender bias for developing vitiligo.

Tumor Necrosis Factor B (TNFB) Genetic Variants and Its Increased Expression Are Associated with Vitiligo Susceptibility