Elif Irmak YAZICI, Hayriye SARICAOĞLU, Şehime Gülsün TEMEL, Emel Bülbül BAŞKAN, Kenan AYDOĞAN, Serkan YAZICI, Güven ÖZKAYA, Haluk Barbaros ORAL
Turkish Journal of Dermatology - 2026;20(3):110-118
Aim: Suppressors of cytokine signaling (SOCS) proteins maintain immune homeostasis and are implicated in autoimmune diseases. This case-control study investigated the role of SOCS1 (rs33989964) and SOCS3 (rs4969168, rs4969170) gene polymorphisms in vitiligo susceptibility, and examined their potential associations with distinct clinical features to evaluate their contribution to phenotypic heterogeneity in vitiligo. Materials and Methods: This study included 100 patients with non-segmental vitiligo and 100 age- and sex-matched healthy controls. Genotyping of SOCS1 (rs33989964) and SOCS3 (rs4969168 and rs4969170) polymorphisms was performed using TaqMan probe-based polymerase chain reaction. A post-hoc power analysis yielded an estimated statistical power of 98.9% for allelic analyses and 96.2% for genotypic analyses, indicating adequate power for the overall analyses. Results: The primary analysis revealed no significant association between SOCS polymorphisms and overall vitiligo susceptibility (P > 0.05). However, uncorrected exploratory subgroup analyses indicated potential clinical correlations: The SOCS1 rs33989964 del/del genotype exhibited a preliminary association with progressive disease [P = 0.025; odds ratio (OR) = 5.27, 95% confidence interval (CI): 1.08-25.78]. For SOCS3 rs4969168, the AA genotype demonstrated a potential, uncorrected association with the absence of triggering factors (P = 0.031) and the Koebner phenomenon (P = 0.049; OR = 4.75, 95% CI: 1.07-21.01), while the A allele was more frequent among patients with familial autoimmunity (P = 0.036; OR = 1.83, 95% CI: 1.03-3.23). Additionally, the SOCS3 rs4969170 AA genotype showed a potential association with poliosis (P = 0.024; OR = 2.77, 95% CI: 1.12-6.85), and its A allele was associated, as an uncorrected exploratory finding, with both poliosis (P = 0.006; OR = 1.97, 95% CI: 1.21-3.22) and leukotrichia (P = 0.048; OR = 1.65, 95% CI: 1.002-2.72). Conclusion: SOCS1 and SOCS3 polymorphisms do not confer overall vitiligo susceptibility. However, these uncorrected exploratory subgroup analyses suggest that they may be associated with adverse clinical features, including progressive disease, familial autoimmunity, Koebner phenomenon, poliosis, and leukotrichia. These findings suggest that SOCS variants may act as modulators of disease phenotype and phenotypic variation rather than susceptibility. These uncorrected associations warrant validation in larger, independent, multivariable cohorts.
