Faculty Collaboration Database

Novel HLA-DP region susceptibility loci associated with severe acute GvHD. Bone Marrow Transplant 2017 Jan;52(1):95-100

Date

09/07/2016

Pubmed ID

27595289

Pubmed Central ID

PMC5215038

DOI

10.1038/bmt.2016.210

Scopus ID

2-s2.0-84991029166 (requires institutional sign-in at Scopus site)   9 Citations

Abstract

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.

Author List

Goyal RK, Lee SJ, Wang T, Trucco M, Haagenson M, Spellman SR, Verneris M, Ferrell RE

Author

Tao Wang PhD Associate Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

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