A CT60G>A polymorphism in the CTLA-4 gene of the recipient may confer susceptibility to acute graft versus host disease after allogeneic hematopoietic stem cell transplantation.
T cell activation plays a crucial role in the development of acute graft versus host disease (aGvHD). Cytotoxic T cell antigen-4 (CTLA-4) is a co-inhibitory molecule that negatively regulates T cell activation, differentiation, and proliferation. Single-nucleotide polymorphisms (SNPs) in CTLA-4 gene may affect its function. Inconsistent observations have been reported regarding the associations of CTLA-4 SNPs with complications after hematopoietic stem cell transplantation (HSCT). Moreover, the majority of the observations were focused on the donors' SNPs. Recently, a few studies have shown that recipients' genetic variations in the CTLA-4 gene might influence HSCT results. The aim of our study was to determine the influence of the CTLA-4 gene polymorphisms of the donors and the recipients on the outcome of HSCT. Altogether, 312 donor-recipient pairs were genotyped for the CTLA-4c.49A>G (rs231775) and CT60G>A (rs3087243) SNPs using the TaqMan®SNP Genotyping Assays. In this study, it was shown that the recipients' CT60G>A[GG] genotype, the myeloablative conditioning regimen, and HSCT from an unrelated donor were independent aGvHD risk factors (odds ratio (OR) 2.63, 95% confidence intervals (95% CI) 1.45-4.59, p = 0.001; OR 2.68, 95% CI 1.65-4.07, p = 0.00003; and OR 1.87, 95 % CI 1.02-3.24, p = 0.04, respectively). Moreover, haplotype analysis revealed that possessing allele A in both of the SNPs decreased the risk of aGvHD approximately 1.5-fold (RR 0.69, p = 0.008). Our data suggest that the CT60G>A[GG] genotype in the recipient has an impact on aGvHD development, especially in patients receiving transplants from unrelated donors together with the myeloablative conditioning regimen.
Department of Experimental Therapy, L. Hirszfeld Institute of Immunology & Experimental Therapy, Polish Academy of Science, R. Weigl 12, 53-114, Wroclaw, Poland, lkarabon@iitd.pan.wroc.pl.
Lidia
L
Karabon
Miroslaw
M
Markiewicz
Anna
A
Partyka
Edyta
E
Pawlak-Adamska
Anna
A
Tomkiewicz
Monika
M
Dzierzak-Mietla
Slawomira
S
Kyrcz-Krzemien
Irena
I
Frydecka
D000293:Adolescent; D000328:Adult; D000483:Alleles; D060908:CTLA-4 Antigen / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D060908:CTLA-4 Antigen