Association between IRAK1 gene polymorphism, gene expression, and non-segmental vitiligo risk in Egyptians

Abstract

Vitiligo is the most prevalent depigmenting skin disorder. Increasing evidence implicates immune dysregulation and inflammatory signaling in its pathogenesis. Interleukin-1 receptor-associated kinase 1 (IRAK1) has been associated with various autoimmune conditions. However, its role in vitiligo remains unexplored. This study investigated the potential relationship between the IRAK1 rs1059703 polymorphism, gene expression, and susceptibility to vitiligo. Genotyping the IRAK1 gene rs1059703 and quantifying its relative expression were assessed using real-time PCR in 123 participants: 53 non-segmental vitiligo patients and 70 healthy volunteers of comparable age and sex. The AA genotype (under the recessive model) was significantly more frequent in vitiligo patients compared to controls (p = 0.032), which increased the risk of vitiligo by an odds ratio of 2.207. Additionally, the A allele demonstrated a notable association with vitiligo risk, with an odds ratio of 1.991. A considerable correlation existed between the AA genotype and a positive family history of vitiligo. IRAK1 expression was markedly more significant in cases versus controls (p < 0.001). Moreover, IRAK1 expression notably correlated with disease duration. The IRAK1 rs1059703 variant, particularly the AA genotype and A allele, along with increased gene expression, may contribute to vitiligo risk. Additional studies with larger cohorts and varied demographics are needed to support these conclusions and elucidate the underlying mechanisms.