Department of Medical Technology, Kagawa Prefectural University of Health Sciences, 281-1 Hara, Mure-cho, Takamatsu, Kagawa, 761-0123, Japan.
Department of Clinical Technology, Hyogo College of Medicine Hospital, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
Immunogenetics. 2018 Jan;70(1):29-36. doi: 10.1007/s00251-017-1014-6. Epub 2017 Jun 26.
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 R-GzmB is a stable protein that accumulates to similar levels in activated NK cells as Q-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.
颗粒酶 B（GzmB）是 NK 细胞溶酶体颗粒中的一种成分，参与多种病理过程。先前已有报道称，GZMB 基因中存在三个非同义编码单核苷酸多态性（rs8192917；Q48R、rs11539752；P88A 和 rs2236338；Y245H），且 QPY/RAH 等位基因簇靠近 C 末端α螺旋。然而，目前尚不清楚 NK 细胞产生的 GzmB 的功能是否受 QPY/RAH 多态性的影响。作者在日本人群（n=106）中研究了 GZMB 基因的 QPY/RAH 多态性分布，以及 Q48R 多态性对 NK 细胞细胞毒性、脱颗粒和 GzmB 产生的影响。这些 SNP 之间存在很强的连锁不平衡，rs8192917（Q48R）影响 NK 细胞的细胞毒性。此外，研究发现 R-GzmB 是一种稳定的蛋白质，在激活的 NK 细胞中积累到与 Q-GzmB 相似的水平。rs8192917 多态性可能影响抗肿瘤活性和抗肿瘤细胞免疫治疗的效果。作者希望这些关于 GZMB 基因 QPY/RAH 多态性的新信息可以帮助评估 NK 细胞细胞毒性在多种病理过程中的影响，并为其治疗提供帮助。
