The impact of costimulatory molecule gene polymorphisms on clinical outcomes in liver transplantation

Brad A. Marder, Bernd Schröppel, Marvin Lin, Thomas Schiano, Rulan Parekh, Yaron Tomer, Barbara Murphy

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

CTLA-4 and CD28 deliver opposing signals for T-cell proliferation. We examined single nucleotide polymorphisms (SNPs) CTLA-4 -318C/T and CD28 IVS3+17T/C for associations with acute rejection in liver transplant recipients. These and two other polymorphisms in CTLA-4 [microsatellite polymorphism +642(AT)n and SNP +49A/G] were also analyzed for influence on graft survival. Two hundred and eleven liver transplant recipient genotypes were determined by direct sequencing or restriction fragment length polymorphism analysis of PCR-amplified genomic DNA. Mean graft survival for patients with the GG genotype of CTLA-4+49 A/G was 58.5±6.0 months compared with 70.3±4.0 months and 73.8±2.8 months 2.8 months for the AA and AG genotypes, respectively (p = 0.0055). This is in support of previous studies suggesting decreased CTLA-4 function and increased incidence of autoimmune disease for this genotype. The 92-, 94-, and 100-bp alleles of CTLA-4+642(AT)n occurred more often in African-American transplant recipients and were associated with decreased graft survival (p = 0.0001 and 0.007, respectively) but the independence of these variables could not be established. No associations with acute rejection or graft survival were found for CTLA-4 -318C/T or CD28 IVS3 + 17T/C. The described associations between CTLA-4 gene polymorphisms and transplant outcomes provide the foundation for further investigations leading to genetic risk stratification for transplant recipients.

Original languageEnglish (US)
Pages (from-to)424-431
Number of pages8
JournalAmerican Journal of Transplantation
Volume3
Issue number4
DOIs
Publication statusPublished - Apr 1 2003
Externally publishedYes

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Keywords

  • Acute rejection
  • CD28
  • CTLA-4
  • Costimulation
  • Graft survival
  • Liver transplant

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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