The Role of REL and IL2 and Their Polymorphisms in the Pathogenesis of Vitiligo-Exploratory Genetic Association Study

Vitiligo is a chronic autoimmune skin disorder characterized by progressive melanocyte loss and depigmented skin lesions, whose pathogenesis has been attributed to genetic and immunological factors. The aim of this exploratory study was to assess REL and IL2 gene expression and evaluate the relationship between the presence of their polymorphisms (rs6545836 and rs2069763) and susceptibility to vitiligo and disease symptoms. The study included 100 patients with vitiligo and 47 healthy controls matched for age and sex. Gene expression in peripheral blood mononuclear cells was assessed using real-time PCR and the ΔΔCT method. Higher REL expression was noted in patients compared with controls (median RQ = 1.52 vs. 1.22), although the difference was not significant (p = 0.919). IL2 gene expression remained below the detection threshold in all analyzed samples. Significant differences in IL2 rs2069763 distribution was found between patients and controls (p = 0.0059, χ² = 7.57, chi-square test; p_adj = 0.02636, Bonferroni correction), with the C allele being more frequent among vitiligo patients and the A allele showing a potential protective effect. Although the CC genotype was initially associated with increased disease risk, this association did not remain significant after correction for multiple comparisons. No significant association between REL rs6545836 and overall susceptibility to vitiligo was identified. Nevertheless, rs6545836 was associated with REL expression levels (Kruskal-Wallis test, p = 0.0032; p_adj = 0.0096, Bonferroni correction). While the overall analysis indicated associations between REL rs6545836 and clinical severity indices (BSA, VES, and VASI), most subgroup associations lost significance after Bonferroni correction; the VASI only demonstrated an insignificant relationship (p_adj = 0.0729). The obtained findings suggest that IL2- and REL-related immune pathways influence vitiligo pathogenesis and clinical heterogeneity; however, these exploratory findings should be interpreted cautiously and require confirmation in studies with greater statistical power.