SG06 TIRAP (rs8177374) single-nucleotide polymorphism in nonsegmental vitiligo associated with metabolic syndrome: a clinical, biochemical and genetic study

Abstract

Vitiligo is an immune-mediated depigmenting disorder of unknown aetiology. Dysregulation of innate immunity and interleukin-17-related inflammatory pathways have been implicated in its pathogenesis. TIR domain-containing adaptor protein (TIRAP/Mal) is a key mediator of Toll-like receptor signalling and may influence autoimmune susceptibility and metabolic dysregulation in nonsegmental vitiligo (NSV). We investigated the association of TIRAP rs8177374 gene polymorphism with susceptibility, clinical characteristics and disease activity in NSV, and assessed its association with metabolic syndrome. This case–control study included 100 patients with active NSV and 100 age- and sex-matched controls. Disease activity and severity were assessed using the Vitiligo Disease Activity score and Vitiligo Area Scoring Index. Fasting lipid profiles and body mass index were obtained. Genotyping of the TIRAP rs8177374 polymorphism was performed using real-time polymerase chain reaction with TaqMan allelic discrimination assays. Significant differences were observed between patients regarding TIRAP rs8177374 genotypes C/T, T/T (odds ratio 6.98, 95% confidence interval 2.89–16.9) and the T allele (odds ratio 9.44, 95% confidence interval 4.16–21.4). The C/T genotype and T allele showed increased susceptibility to vitiligo by sevenfold and ninefold, respectively. The C/T and T/T genotypes were associated with high body mass index (P = 0.03 and P = 0.01, respectively) and increased triglyceride level (P = 0.007 and P = 0.002, respectively). TIRAP rs8177374 genotypes showed a significant association with disease activity, but not severity. The TIRAP rs8177374 polymorphism is strongly associated with susceptibility and activity of NSV, with an increased likelihood of metabolic dysregulation. These findings support a pathogenic role for innate immune signalling via TIRAP and highlight its potential as a biomarker for disease risk and activity. Further investigation of the interleukin-17 pathway in vitiligo is warranted.