Evaluation of +49 A>G (rs231775) Variant in CTLA4 Gene and SCTLA-4 Serum Levels in Plaque Psoriasis in a Mestizo Mexican Population

Int J Mol Sci. 2026 Apr 1;27(7):3202. doi: 10.3390/ijms27073202.

Abstract

Plaque psoriasis (PP) is a chronic immune-mediated skin disorder characterized by T-cell dysregulation and an imbalance between regulatory T cells (Treg) and T helper 17 (Th17) cells. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), a key inhibitory checkpoint molecule expressed on Treg cells, and its soluble isoform (sCTLA-4) are critical regulators of peripheral immune tolerance and may contribute to PP pathogenesis. This case-control study evaluated the association between the +49 A>G variant of the CTLA4 gene (rs231775) and susceptibility to PP in a mestizo population from western Mexico and assessed serum sCTLA-4 levels. A total of 204 patients with PP and 214 control subjects (CS) were genotyped using PCR-RFLP, and sCTLA-4 concentrations were measured by ELISA. The AG genotype was the most frequent in both groups (49% in PP and 53% in CS), with no significant differences in genotype or allele distributions. Serum sCTLA-4 levels were significantly higher in CS compared to patients (p < 0.05), and no genotype-dependent differences were observed. The rs231775 variant was not associated with PP susceptibility in this population. However, reduced circulating sCTLA-4 levels in patients suggest impaired CTLA-4-mediated immune regulation independent of this variant.

Keywords: CTLA4 variant; genetic susceptibility; immune checkpoint; plaque psoriasis; rs231775; soluble CTLA-4.

MeSH terms

  • Adult
  • Alleles
  • CTLA-4 Antigen* / blood
  • CTLA-4 Antigen* / genetics
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Mexico / epidemiology
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Psoriasis* / blood
  • Psoriasis* / genetics

Substances

  • CTLA-4 Antigen
  • CTLA4 protein, human