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Published on: August 12, 2017
Effect of CTLA-4 gene polymorphisms on long-term kidney allograft function in Han Chinese recipients
Yifeng Guo1, Junwei Gao2, Shuai Gao1
1Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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.
Insights
Specific single nucleotide polymorphisms (SNPs) in the CTLA-4 gene are linked to kidney transplant success. Certain CTLA-4 genotypes and haplotypes predict long-term allograft function in Chinese recipients.
Area of Science:
- Immunogenetics
- Transplantation immunology
- Renal medicine
Background:
- Single nucleotide polymorphisms (SNPs) in the cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) gene are implicated in organ transplant outcomes.
- Understanding genetic factors influencing long-term allograft function is crucial for improving patient prognosis.
Purpose of the Study:
- To investigate the association between specific CTLA-4 gene SNPs (rs733618, rs4553808, rs5742909, rs231775, rs3087243) and long-term kidney allograft function.
- To identify genetic markers that may predict the success of renal transplantation in a Chinese population.
Main Methods:
- Genotyping of five CTLA-4 SNPs was performed in 292 Chinese renal transplant recipients.
- Long-term allograft function was assessed by measuring estimated glomerular filtration rate (eGFR) at multiple time points up to 60 months post-transplantation.
- Haplotype analysis was conducted to evaluate combinations of SNPs.
Main Results:
- Significant associations were found between CTLA-4 SNPs rs733618, rs3087243 (alleles and genotypes), and rs5742909, rs231775 (genotypes) with long-term allograft function (P<0.05).
- Favorable genotypes correlated with enhanced allograft function over the 60-month follow-up period.
- Specific haplotypes (TACGG, CACAG, CGTAA) were also significantly associated with kidney function (P<0.05 or P<0.01).
Conclusions:
- Certain CTLA-4 genotypes (e.g., rs5742909TT) and alleles (e.g., rs733618C, rs3087243A) are associated with better long-term allograft function.
- Unfavorable genotypes (e.g., rs733618TT, rs3087243GG, rs231775GG) and the TACGG haplotype may indicate poorer outcomes.
- These CTLA-4 genetic variants and haplotypes could serve as predictive indicators for long-term kidney allograft function in Chinese recipients.
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