Recipient ctla-4 +49 G/G genotype is associated with reduced incidence of acute rejection after liver transplantation.
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.
de Reuver
Philip
P
Department of Gastroenterology, Erasmus Medical Centre, Rotterdam, the Netherlands.
Pravica
Vera
V
Hop
Wim
W
Boor
Patrick
P
Metselaar
Herold J
HJ
Hutchinson
Ian V
IV
Tilanus
Hugo W
HW
Kwekkeboom
Jaap
J
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
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