title: Risk of adverse post-transplant events after kidney allograft transplantation as predicted by CTLA-4 +49 and TNF-alpha -308 single nucleotide polymorphisms: a preliminary study.
abstract: Genetic differences between donor and recipient HLA haplotypes are of major importance for transplant rejection. Other genetic variations occurring in genes encoding cytokines and costimulatory molecules also appear to exert an influence on the manner the host immune system recognizes the allograft. The aims of this work were: 1) to study selected single nucleotide polymorphisms (SNPs) at the loci encoding the T-cell regulatory molecule CTLA-4 (CD152), and the cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-beta1 in a sample of healthy volunteers and a group of kidney-transplanted patients; and 2) to investigate whether an association exists between any of the SNPs studied and acute or chronic rejection, or non-responsiveness to steroid treatment during episodes of acute rejection (AR) after kidney allograft transplantation. When healthy volunteers were compared with transplanted patients, no significant differences were found in the distribution of genetic frequencies for any of the SNPs analyzed. However, in transplanted patients who received a kidney from a living related donor (KdTxL), a statistically significant association was found between carrying the CTLA-4 +49 A/A genotype and protection from experiencing acute rejection. No such association was found in the group of transplanted patients who received a kidney from a cadaveric non-related donor (KdTxCad). In both, KdTxL and KdTxCad patients, responsiveness to steroid treatment during acute rejection was also in association with the CTLA-4 (+49A/G) SNP. The CTLA-4 +49G allele was found at a very low frequency among steroid-resistant compared with steroid-sensitive patients. Finally, a statistically significant association was found between the presence of the TNF-alpha -308A allele and protection to suffer from chronic rejection. The genetic differences found may serve as risk predictors of adverse post-transplant events.
authors.affiliation: Laboratorio de Fisiopatología, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Caracas, Venezuela.
authors.forename: Ketevan
authors.initials: K
authors.lastname: Gendzekhadze
authors.forename: Pedro
authors.initials: P
authors.lastname: Rivas-Vetencourt
authors.forename: Ramón F
authors.initials: RF
authors.lastname: Montano
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D005819:Genetic Markers; D006084:Graft Rejection / Q000235:genetics*; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D005819:Genetic Markers; D014409:Tumor Necrosis Factor-alpha