title: Recipient ctla-4 +49 G/G genotype is associated with reduced incidence of acute rejection after liver transplantation.
abstract: The aim of this pilot study was to investigate whether acute rejection after liver transplantation is associated with known single-nucleotide polymorphisms (SNPs) in the CD86- and CTLA-4 genes of liver-transplant donors and recipients. Single nucleotide polymorphisms were determined in 135 liver transplant recipients and in 73 donors. Acute rejection was not associated with CD86 + 1057 G/A genotype distributions in donors and in recipients. In univariate analysis recipient CTLA-4 -318 G/T and + 49 A/G genotype distributions were both weakly associated with acute rejection. Multivariate analysis revealed that the CTLA-4 + 49 SNP, but not the -318 SNP, was independently of other risk factors associated with acute rejection. Only one out of 13 CTLA-4 + 49 G-homozygotes (8%) experienced acute rejection(s) compared with 40% of A/A or A/G recipients. The CTLA-4 + 49 A/G SNP, which results in an amino acid substitution in the signal peptide of the protein, did not, however, affect intracellular expression or trafficking of CTLA-4 in T cells, nor soluble serum CTLA-4 concentrations of the liver transplant recipients. In conclusion, this pilot study suggests that liver transplant recipients homozygous for CTLA-4 + 49 G have a reduced risk of acute rejection.
authors: Department of Gastroenterology, Erasmus Medical Centre, Rotterdam, the Netherlands.
authors: Philip
authors: P
authors: de Reuver
authors: Vera
authors: V
authors: Pravica
authors: Wim
authors: W
authors: Hop
authors: Patrick
authors: P
authors: Boor
authors: Herold J
authors: HJ
authors: Metselaar
authors: Ian V
authors: IV
authors: Hutchinson
authors: Hugo W
authors: HW
authors: Tilanus
authors: Jaap
authors: J
authors: Kwekkeboom
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D000943:Antigens, Differentiation / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; D005260:Female; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008099:Liver / Q000276:immunology*; D016031:Liver Transplantation; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D051940:B7-2 Antigen; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D008562:Membrane Glycoproteins