Effect of CTLA-4 gene polymorphisms on long-term kidney allograft function in Han Chinese recipients

Oncotarget. 2016 Apr 26;7(17):23088-95. doi: 10.18632/oncotarget.8714.

Abstract

Single nucleotide polymorphisms (SNPs) of cytotoxic T lymphocyte associated antigen-4 gene (CTLA-4) have been associated with graft rejection and long-term clinical outcome after organ transplantation. Our aim was to examine the association between CTLA-4 SNPs (rs733618, rs4553808, rs5742909, rs231775, rs3087243) and long-term allograft function in Chinese renal transplant recipients. Genotyping of CTLA-4 SNPs was performed in 292 renal transplantation recipients. To assess long-term allograft function, the estimated glomerular filtration rate (eGFR) was determined 1, 3, 6, 12, 24, 36, 48 and 60 months after renal transplantation. CTLA-4 rs733618 and rs3087243 alleles and genotypes as well as the rs5742909 and rs231775 genotypes were significantly associated with long-term allograft function after transplantation (P<0.05). Patients with favorable genotypes had higher allograft function during the 60 months after transplantation. The TACGG, CACAG and CGTAA haplotypes were also associated with long-term kidney function after renal transplantation (P<0.05 or P<0.01). In sum, the favorable CTLA-4 rs5742909TT genotype, CTLA-4 rs733618C and rs3087243A alleles, and CACAG and CGTAA haplotypes, as well as the unfavorable rs733618TT, rs3087243GG and rs231775GG genotypes and TACGG haplotype could potentially serve as effective indicators of long-term allograft function in Chinese renal transplantation recipients.

Keywords: Pathology Section; cytotoxic T lymphocyte associated antigen-4; estimated glomerular filtration rate; gene polymorphism; kidney transplant; long-term allograft function.

MeSH terms

  • Allografts
  • Asian People / genetics*
  • Biomarkers / metabolism*
  • CTLA-4 Antigen / genetics*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Graft Rejection / etiology*
  • Graft Rejection / pathology
  • Humans
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*

Substances

  • Biomarkers
  • CTLA-4 Antigen