Abstract
The genetic background of donor and recipient is an important factor determining the outcome of allogeneic hematopoietic SCT (allo-HSCT). We applied 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 (SNPs) 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 a novel immunogenetic factor associated with graft rejection in patients undergoing allo-HSCT.
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05 November 2014
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
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Acknowledgements
This work was supported by the Mediterranean Institution of Hematology Foundation (IME), Bioflag Srl. internal development funds, and Telethon Italy grant number TGT11A03.
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Piras, I., Angius, A., Andreani, M. et al. BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA-related SCT. Bone Marrow Transplant 49, 1400–1404 (2014). https://doi.org/10.1038/bmt.2014.177
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DOI: https://doi.org/10.1038/bmt.2014.177