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The Impact of Costimulatory Molecule Gene Polymorphisms on Clinical Outcomes in Liver Transplantation
Author(s) -
Marder Brad A.,
Schröppel Bernd,
Lin Marvin,
Schiano Thomas,
Parekh Rulan,
Tomer Yaron,
Murphy Barbara
Publication year - 2003
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1034/j.1600-6143.2003.00084.x
Subject(s) - genotype , single nucleotide polymorphism , allele , medicine , transplantation , liver transplantation , immunology , snp , ctla 4 , restriction fragment length polymorphism , gastroenterology , gene , genetics , biology , t cell , immune system
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 +49 A/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 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 .