title: Association of genetic variation in co-stimulatory molecule genes with outcome of liver transplant in Iranian patients.
abstract: CD28, cytotoxic T-lymphocyte associated antigen 4 (CTLA4), inducible costimulator (ICOS) and programmed cell death 1 are closely-linked genes located on chromosome 2q and encode co-stimulatory molecules, which are T-cell activity regulators. The principal assignment of T-cell mediated immune response in allograft rejection is an interesting topic of multiple studies. Although the variation in these genes may influence the graft survival and the amount of immunosuppression needed, the studies so far have been restricted solely to the CTLA4 gene. In 145 patients who underwent liver allograft transplantation, 10 single nucleotide polymorphisms of CD28, CTLA4, ICOS, and PD.1 genes were defined. To distinguish the polymorphisms of all 10 SNPs, PCR-RFLP method was used and according to the standard criteria, acute rejection episodes were determined. CTLA4-1661, AA genotype was significantly more frequent in the patients with acute rejection and AG genotype was significantly more frequent in the patients without rejection. Frequencies of CTLA4+49 AG A allele and CTLA4-1661AG A allele were significantly higher than those of CTLA4+49 AG and CTLA4-1661AG, G allele in the patients with acute rejection. ICOS+693, GG genotype and G allele were significantly less frequent in the patients with acute rejection and CD28 CT genotype was significantly more in patients with acute rejection. The present results demonstrate that potentially functional genetic variation in T-cell co-stimulatory molecules including ICOS, CTLA4 and CD28 can influence liver transplant outcome.
authors.affiliation: Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Karimimh@sums.ac.ir
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Karimi
authors.forename: Maryam
authors.initials: M
authors.lastname: Motazedian
authors.forename: Fariba
authors.initials: F
authors.lastname: Abedi
authors.forename: Ramin
authors.initials: R
authors.lastname: Yaghobi
authors.forename: Bita
authors.initials: B
authors.lastname: Geramizadeh
authors.forename: Saman
authors.initials: S
authors.lastname: Nikeghbalian
mesh_terms: D000328:Adult; D018106:CD28 Antigens / Q000235:genetics*; D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006084:Graft Rejection / Q000235:genetics*; D006085:Graft Survival / Q000235:genetics; D006801:Humans; D060889:Inducible T-Cell Co-Stimulator Protein / Q000235:genetics*; D007492:Iran; D016031:Liver Transplantation; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556692:ICOS protein, human; D060889:Inducible T-Cell Co-Stimulator Protein; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor