Genotypes and haplotypes in the 3′ untranslated region of the HLA-G gene and their association with clinical outcome of hematopoietic stem cell transplantation for beta-thalassemia
| Autor: | Antonio Amoroso, Benedetta Mazzi, Federico Sizzano, M Torchio, C Pultrone, Fabio Ciceri, Maria Troiano, Robert Chiesa, Sarah Marktel, Katharina Fleischhauer, M. G. Roncarolo, Laura Zito, Javid Gaziev, Roberto Crocchiolo, Silvia Gregori, Guido Lucarelli, Manuela Testi, G Turchiano, Pietro Sodani, Marco Andreani |
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| Přispěvatelé: | Sizzano, F, Testi, M, Zito, L, Crocchiolo, R, Troiano, M, Mazzi, B, Turchiano, G, Torchio, M, Pultrone, C, Gregori, S, Chiesa, R, Gaziev, J, Sodani, P, Marktel, S, Amoroso, A, Roncarolo, MARIA GRAZIA, Lucarelli, G, Ciceri, Fabio, Andreani, M, Fleischhauer, K. |
| Rok vydání: | 2012 |
| Předmět: |
Adult
Male Linkage disequilibrium Adolescent Genotype medicine.medical_treatment Immunology Graft vs Host Disease Single-nucleotide polymorphism Hematopoietic stem cell transplantation Human leukocyte antigen Biology Biochemistry Linkage Disequilibrium Immune Tolerance Genetics medicine Humans Transplantation Homologous Immunology and Allergy Child 3' Untranslated Regions Sequence Deletion HLA-G Antigens Polymorphism Genetic Siblings beta-Thalassemia Haplotype Hematopoietic Stem Cell Transplantation Beta thalassemia General Medicine medicine.disease Transplantation Mutagenesis Insertional Treatment Outcome Haplotypes Italy Case-Control Studies Child Preschool Female |
| Zdroj: | Tissue Antigens. 79:326-332 |
| ISSN: | 0001-2815 |
| Popis: | Polymorphisms in the 3' untranslated region (3'UTR) of HLA-G, an important player in immunological tolerance, could be involved in post-transcriptional expression control, and their association with different clinical immune-related conditions including autoimmunity and transplantation is of mounting interest. Most studies have focused on a 14 base pair (bp) insertion/deletion (ins/del), while additional single-nucleotide polymorphisms (SNPs) in the HLA-G 3'UTR have been described but not extensively investigated for their clinical relevance. Here we have comparatively studied the association between 3'UTR haplotypes of HLA-G, or the 14 bp ins/del, with clinical outcome of HLA-identical sibling hematopoietic stem cell transplantation (HSCT) in 147 Middle Eastern beta-thalassemia patients. Sequence based typing of 3'UTR HLA-G polymorphisms in the patients and in 102 healthy Italian blood donors showed strong linkage disequilibrium between the 14 bp ins/del and five 3'UTR SNPs, which together could be arranged into eight distinct haplotypes based on expectation-maximization studies, with four predominant haplotypes (UTRs1-4). After HSCT, we found a moderate though not significant association between the presence of UTR-2 in double dose and protection from acute graft versus host disease (hazard ratio (HR) 0.45, 95% confidence intervals (CI): 0.14-1.45; P = 0.18), an effect that was also seen when the corresponding 14 bp ins/ins genotype was considered alone (HR 0.42, 95% CI: 0.16-1.06; P = 0.07). No association was found with rejection or survival. Taken together, our data show that there is no apparent added value of considering entire 3'UTR HLA-G haplotypes for risk prediction after allogeneic HSCT for beta-thalassemia. |
| Databáze: | OpenAIRE |
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