BAT2 and BAT3 polymorphisms as novel genetic risk factors for rejection after HLA-related SCT

Bone Marrow Transplant. 2014 Nov;49(11):1400-1404. doi: 10.1038/bmt.2014.177. Epub 2014 Aug 11.

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 (R(2)=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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Allografts
  • Child
  • Child, Preschool
  • Female
  • Genome-Wide Association Study
  • Graft Rejection / genetics*
  • HLA Antigens
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Male
  • Molecular Chaperones / genetics*
  • Polymorphism, Single Nucleotide*
  • Proteins / genetics*
  • Risk
  • Risk Factors
  • beta-Thalassemia* / genetics
  • beta-Thalassemia* / therapy

Substances

  • BAG6 protein, human
  • HLA Antigens
  • Molecular Chaperones
  • Proteins
  • PRRC2A protein, human