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.

Comprehensive Analysis of 29,464 Cancer Cases and 35,858 Controls to Investigate the Effect of the Cytotoxic T-Lymphocyte Antigen 4 Gene rs231775 A/G Polymorphism on Cancer Risk

“…In addition, Gouda et al. reported that the genotype (GG) was associated with relatively lower CTLA-4 expression levels than the other genotypes (like GC or CC) ( 11 ). To evaluate the effects of the functional SNP and cancer susceptibility, we carried out genotyping analyses among rs231775 A/G in 29,464 cases and 35,858 controls.…”

Association between the CTLA4 +49A/G (rs231775) and CT60 (rs3087243) gene variants with vitiligo: study on a Mexican population

“… 10 However, these variants and their association with vitiligo vary widely and seem to be heavily dependent upon the analyzed population. 10 , 11 , 12…”