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QPY/RAH haplotypes of the GZMB gene are associated with natural killer cell cytotoxicity

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Abstract

Granzyme B (GzmB) is a component of cytolytic granules within NK cells and is involved in several pathologies. It has previously been reported that there are three non-synonymous coding SNPs (rs8192917; Q48R, rs11539752; P88A, and rs2236338; Y245H) in the GZMB gene and that the QPY/RAH allele was clustered together close to the C-terminal α-helix. However, it is unknown whether the function of GzmB produced from NK cells is influenced by QPY/RAH polymorphism. The authors investigated the distribution of QPY/RAH polymorphism of the GZMB gene in a Japanese population (n = 106), and the involvement of Q48R polymorphism in NK cell cytotoxicity, degranulation, and production of GzmB. A strong linkage disequilibrium was observed among these SNPs, and NK cell cytotoxicity was influenced by rs8192917 (Q48R). Moreover, it found that R48-GzmB is a stable protein that accumulates to similar levels in activated NK cells as Q48-GzmB. rs8192917 polymorphism may influence antitumor activity and the effect of antitumor cellular immunotherapy. The authors expect that these new informations about QPY/RAH polymorphism of the GZMB gene could help to assess the impact of NK cell cytotoxicity in several pathologies and aid their treatment.

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Authors and Affiliations

  1. Department of Medical Technology, Kagawa Prefectural University of Health Sciences, 281-1 Hara, Mure-cho, Takamatsu, Kagawa, 761-0123, Japan

    Wataru Oboshi, Takehiro Nakamura & Nobuyasu Yukimasa

  2. Department of Clinical Technology, Hyogo College of Medicine Hospital, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

    Toru Watanabe

  3. The Graduate School of Health Sciences, Kagawa Prefectural University of Health Sciences, 281-1 Hara, Mure-cho, Takamatsu, Kagawa, 761-0123, Japan

    Keisuke Hayashi

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  1. Wataru Oboshi
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  2. Toru Watanabe
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  3. Keisuke Hayashi
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  4. Takehiro Nakamura
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  5. Nobuyasu Yukimasa
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Correspondence to Takehiro Nakamura.

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The study protocol was approved by the Ethics Committee of Kagawa Prefectural University of Health Sciences, and written consent was obtained from all participating subjects according to the Declaration of Helsinki.

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Oboshi, W., Watanabe, T., Hayashi, K. et al. QPY/RAH haplotypes of the GZMB gene are associated with natural killer cell cytotoxicity. Immunogenetics 70, 29–36 (2018). https://doi.org/10.1007/s00251-017-1014-6

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  • DOI: https://doi.org/10.1007/s00251-017-1014-6

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