Impact of cytotoxic T‐lymphocyte‐associated protein 4 codon 17 variant and expression on vitiligo risk

Abstract Background Cytotoxic T‐lymphocyte‐associated protein 4 (CTLA‐4) is one of the essential brakes expressed on T cells that prevent T‐cell hyperactivation‐associated autoimmune disorders. Several CTLA4 polymorphisms were implicated in the regulation of gene expression. We aimed to explore the association of CTLA4 expression and rs231775 (c.49A>G) variant with vitiligo risk and severity of the disease in a sample of the Middle Eastern population. Methods The CTLA4 gene expression and genotyping for rs231775 (A/G) variant were assessed in 161 vitiligo patients and 165 controls using a real‐time polymerase chain reaction. Vitiligo Area Severity Index (VASI) and Vitiligo Disease Activity score (VIDA) were evaluated. Results A higher frequency of rs231775 G allele was observed in vitiligo cases than controls (45% vs. 33%, p  = 0.002). After adjustment of age, sex, family history of vitiligo, and CTLA expression level, using multivariate analysis, G/G carriers were associated with a higher risk of vitiligo under recessive (OR = 2.94, 95% CI = 1.61–5.35, p  < 0.001), dominant (OR = 1.87, 95% CI = 1.14–3.06, p  = 0.013), and homozygote comparison (OR = 3.34, 95% CI = 1.73–6.42, p  = 0.001) models. Although the CTLA4 relative expression levels were comparable to that of controls, G/G carriers exhibited a significantly lower expression profile (median = 0.63, IQR = 0.34–1.75) than A/A (median = 1.43, IQR = 0.39–4.25, p  = 0.018) and A/G carriers (median = 1.68, IQR = 0.49–3.92, p  = 0.007). No significant associations of CTLA4 variant/expression with disease severity and/or activity were observed. Conclusion The CTLA4 rs231775 variant was associated with vitiligo susceptibility and gene expression; the risky genotype (GG) was associated with lower CTLA4 relative expression levels than the other genotypes. Further large‐scale studies in different populations are warranted.