1. BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA-related SCT
- Author
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Guido Lucarelli, Ignazio S. Piras, G. La Nasa, Alessandro Bulfone, Silvia Gregori, Rosa Bacchetta, Sarah Marktel, Maria Grazia Roncarolo, Marco Andreani, Manuela Testi, Katharina Fleischhauer, Andrea Angius, Matteo Floris, Fabio Ciceri, Piras, I, Angius, A, Andreani, M, Testi, M, Lucarelli, G, Floris, M, Marktel, S, Ciceri, Fabio, La Nasa, G, Fleischhauer, K, Roncarolo, Mg, Bulfone, A, Gregori, S, and Bacchetta, R.
- Subjects
Adult ,Graft Rejection ,Male ,Risk ,Adolescent ,medicine.medical_treatment ,Genome-wide association study ,Human leukocyte antigen ,Hematopoietic stem cell transplantation ,Polymorphism, Single Nucleotide ,whole genome analysis ,Article ,immune system diseases ,HLA Antigens ,Risk Factors ,hemic and lymphatic diseases ,BAT3 ,medicine ,BAT2 ,Humans ,Genetic risk ,Child ,Allogeneic hematopoietic stem transplantation ,Transplantation ,Graft rejection ,business.industry ,beta-Thalassemia ,Hematopoietic Stem Cell Transplantation ,Beta thalassemia ,Proteins ,Hematology ,medicine.disease ,Allografts ,surgical procedures, operative ,Graft-versus-host disease ,Child, Preschool ,Immunology ,Female ,business ,therapeutics ,human activities ,Genome-Wide Association Study ,Molecular Chaperones - Abstract
The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We applied a whole genome analysis to investigate genetic variants - other than HLA class I and II - associated with negative outcome after HLA-identical sibling allo-HSCT in a cohort of 110 β-Thalassemic patients. We identified two single nucleotide polymorphisms in BAT2 (A/G) and BAT3 (T/C) genes, SNP rs11538264 and SNP rs10484558, both located in the HLA class III region, in strong Linkage Disequilibrium between each other (R2=0.92). When considered as single SNP, none of them reached a significant association with graft rejection (nominal P < 0.00001 for BAT2 SNP rs11538264, and P < 0.0001 for BAT3 SNP rs10484558). Whereas, the BAT2/BAT3 A/C haplotype was present at significantly higher frequency in patients who rejected as compared to those with functional graft (30.0% vs. 2.6%, nominal P = 1.15×10−8; and adjusted P = 0.0071). The BAT2/BAT3 polymorphisms and specifically the A/C haplotype may represent novel immunogenetic factor associated with graft rejection in patients undergoing allo-HSCT.
- Published
- 2013