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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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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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Acknowledgment

A Health Science Research Grant from the Ministry of Labor and Welfare of Japan supported this study.

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Authors and Affiliations

  1. Department of Pathology, Sapporo Medical University School of Medicine, Hokkaido, Japan

    Tomoki Kikuchi, Shingo Ichimiya & Noriyuki Sato

  2. Department of Molecular Pathogenesis, Division of Pathophysiology Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

    Taeko K. Naruse

  3. Department of Molecular Life Science, Course of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Kanagawa, Japan

    Tomoki Kikuchi, Suyun Li, Tetsuaki Kimura, Akira Oka, Jerzy K. Kulski & Hidetoshi Inoko

  4. Department of Hematology and Oncology, Tokai University School of Medicine, Kanagawa, Japan

    Makoto Onizuka

  5. Department of Hematology and Cell Therapy, Aichi Cancer Center, Aichi, Japan

    Yasuo Morishima

  6. Centre for Comparative Genomics, School of Information Technology, Murdoch University, Murdoch, Western Australia, Australia

    Jerzy K. Kulski

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  1. Tomoki Kikuchi
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  3. Makoto Onizuka
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  4. Suyun Li
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  6. Akira Oka
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  7. Yasuo Morishima
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  9. Shingo Ichimiya
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  10. Noriyuki Sato
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  11. Hidetoshi Inoko
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Correspondence to Hidetoshi Inoko.

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Kikuchi, T., Naruse, T.K., Onizuka, M. et al. 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. Immunogenetics 59, 99–108 (2007). https://doi.org/10.1007/s00251-006-0186-2

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