PMCID: PMC5215038 DOI: 10.1038/bmt.2016.210
Despite HLA allele matching, significant acute GvHD remains a major barrier to successful unrelated donor BMT. We conducted a genome-wide association study (GWAS) to identify recipient and donor genes associated with the risk of acute GvHD. A case-control design (grade III-IV versus no acute GvHD) and pooled GWA approach was used to study European-American recipients with hematological malignancies who received myeloablative conditioning non-T-cell-depleted first transplantation from HLA-A, -B, -C, -DRB1, -DQB1 allele level (10/10) matched unrelated donors. DNA samples were divided into three pools and tested in triplicate using the Affymetrix Genome-wide SNP Array 6.0. We identified three novel susceptibility loci in the HLA-DP region of recipient genomes that were associated with III-IV acute GvHD (rs9277378, P=1.58E-09; rs9277542, P=1.548E-06 and rs9277341, P=7.718E-05). Of these three single nucleotide polymorphisms (SNPs), rs9277378 and rs9277542 are located in non-coding regions of the HLA-DPB1 gene and the two are in strong linkage disequilibrium with two other published SNPs associated with acute GvHD, rs2281389 and rs9277535. Eighteen other recipient SNPs and 3 donor SNPs with a high level of significance (8E-07 or lower) were found. Our report contributes to emerging data showing clinical significance of the HLA-DP region genetic markers beyond structural matching of DPB1 alleles.
Bone marrow transplantation
Acute Disease; Adolescent; Adult; Aged; Alleles; Allografts; Bone Marrow Transplantation; Child; Child, Preschool; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Graft vs Host Disease; HLA-DP beta-Chains; Hematologic Neoplasms; Humans; Infant; Linkage Disequilibrium; Male; Middle Aged; Polymorphism, Single Nucleotide; Unrelated Donors
BMT; GvHD; Babies; Children; Teenagers
Goyal, Rakesh K.; Lee, S J.; Wang, T; Trucco, M; Haagenson, M; Spellman, S R.; Verneris, M; and Ferrell, R E., "Novel HLA-DP region susceptibility loci associated with severe acute GvHD." (2017). Manuscripts, Articles, Book Chapters and Other Papers. 503.