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

• Published in: Immunogenetics (New York) Vol. 67; no. 5-6; pp. 295 - 304
• Main Authors: Karabon, Lidia, Markiewicz, Miroslaw, Partyka, Anna, Pawlak-Adamska, Edyta, Tomkiewicz, Anna, Dzierzak-Mietla, Monika, Kyrcz-Krzemien, Slawomira, Frydecka, Irena
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2015; Springer Nature B.V
• Subjects: Adolescent; Adult; Alleles; Allergology; Antigens; Biomedical and Life Sciences; Biomedicine; Blood diseases; Bone marrow; Cell Biology; Cell cycle; CTLA-4 Antigen - genetics; Cytotoxicity; Female; Gene Function; Genes; Genetic Association Studies; Genetic diversity; Genotype; Genotype & phenotype; Graft versus host disease; Graft vs Host Disease - genetics; Graft vs Host Disease - immunology; Graft vs Host Disease - pathology; Haplotypes; Hematology; Hematopoietic Stem Cell Transplantation - adverse effects; Human Genetics; Humans; Immunology; Lymphocytes; Male; Middle Aged; Original Paper; Polymorphism; Polymorphism, Single Nucleotide; Proteins; Risk Factors; Stem cell transplantation; Stem cells; Poland; Acute graft versus host disease; CTLA-4; Gene polymorphism; Hematopoietic stem cell transplantation
• ISSN: 0093-7711; 1432-1211
• DOI: 10.1007/s00251-015-0840-7

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-4 c.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.