2. Academic Validation
  3. Impact of cytotoxic T-lymphocyte-associated protein 4 codon 17 variant and expression on vitiligo risk

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

  • J Clin Lab Anal. 2021 Jun;35(6):e23777. doi: 10.1002/jcla.23777.
Nawal S Gouda 1 2,  Manal S Fawzy 3 4,  Eman A Toraih 5 6
Affiliations

Affiliations

  • 1 Department of Medical Microbiology and Immunology, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia.
  • 2 Department of Medical Microbiology and Immunology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
  • 3 Department of Medical Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia.
  • 4 Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
  • 5 Department of Surgery, School of Medicine, Tulane University, New Orleans, LA, USA.
  • 6 Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
PMID: 33932254 DOI: 10.1002/jcla.23777
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.

Keywords

CTLA4; gene expression; polymorphism; real-time PCR; rs231775; vitiligo.

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