Mapping of susceptibility and protective loci for acute GVHD in unrelated HLA-matched bone marrow transplantation donors and recipients using 155 microsatellite markers on chromosome 22 |
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Authors: | Tomoki Kikuchi Taeko K Naruse Makoto Onizuka Suyun Li Tetsuaki Kimura Akira Oka Yasuo Morishima Jerzy K Kulski Shingo Ichimiya Noriyuki Sato Hidetoshi Inoko |
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Institution: | (1) Department of Pathology, Sapporo Medical University School of Medicine, Hokkaido, Japan;(2) Department of Molecular Pathogenesis, Division of Pathophysiology Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan;(3) Department of Molecular Life Science, Course of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Kanagawa, Japan;(4) Department of Hematology and Oncology, Tokai University School of Medicine, Kanagawa, Japan;(5) Department of Hematology and Cell Therapy, Aichi Cancer Center, Aichi, Japan;(6) Centre for Comparative Genomics, School of Information Technology, Murdoch University, Murdoch, Western Australia, Australia |
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Abstract: | Despite matching donors and recipients for the human leukocyte antigens (HLAs) expressed by the major histocompatibility genomic
region of the short arm of chromosome 6, several recipients still develop acute graft-versus-host disease (aGVHD) after bone
marrow transplantation (BMT). This is possibly due to non-HLA gene polymorphisms, such as minor histocompatibility antigens
(mHas) and genes coding for cytokines. However, a detailed genetic background for aGVHD has not yet been established. To find
novel susceptibility and/or protective loci for aGVHD, a whole genome-wide association study of donors and recipients needs
to be performed. As the first step to such a study, we retrospectively analyzed polymorphisms of 155 microsatellite markers
spread across the long arm of chromosome 22 in 70 pairs of HLA-matched unrelated BMT donors and recipients. We performed individual
typing and then compared the markers’ allele frequencies (1) between all the aGVHD (grades III and IV GVHD) and GVHD-free
(grade 0 GVHD) groups in donors and recipients and (2) between the aGVHD and aGVHD-free groups in donor/recipient pairs that
were matched and mismatched for the microsatellite marker’s allele. Screening of the microsatellite markers revealed five
loci with a significant difference between the aGVHD and GVHD-free groups and revealed eight loci on chromosome 22, where
the microsatellite allele mismatched markers were associated with aGVHD. This screening analysis suggests that several aGVHD-associated
susceptible and protective loci exist on chromosome 22, which may encompass novel gene regions that need to be elucidated
for their role in aGVHD. |
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Keywords: | Microsatellite Bone marrow transplantation Acute GVHD Chromosome 22 Non-HLA |
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