杀伤细胞免疫球蛋白样受体多态性与胶质母细胞瘤风险

Polymorphisms of Killer Ig-like Receptors and the Risk of Glioblastoma.

作者信息

Choi Haeyoun, Baek In-Cheol, Park Soon A, Park Jae-Sung, Jeun Sin-Soo, Kim Tai-Gyu, Ahn Stephen

机构信息

Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.

Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.

出版信息

J Clin Med. 2023 Jul 19;12(14):4780. doi: 10.3390/jcm12144780.

DOI:10.3390/jcm12144780

PMID:37510895

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10380963/

Abstract

PURPOSE

The immune responses of natural killer (NK) cells against cancer cells vary by patient. Killer Ig-like receptors (KIRs), which are some of the major receptors involved in regulating NK cell activity for killing cancer cells, have significant genetic variation. Numerous studies have suggested a potential association between the genetic variation of KIR genes and the risk of development or prognosis of various cancer types. However, an association between genetic variations of KIR genes and glioblastoma (GB) remains uncertain. We sought to evaluate the association of genetic variations of KIRs and their ligand genes with the risk of GB development in Koreans.

METHODS

A case-control study was performed to identify the odds ratios (ORs) of KIR genes and Classes A, B, and, C of the human leukocyte antigen (HLA) for GB. The GB group was comprised of 77 patients with newly diagnosed IDH-wildtype GB at our institution, and the control group consisted of 200 healthy Korean volunteers.

RESULTS

There was no significant difference in the frequency of KIR genes and KIR haplotypes between the GB and control groups. Genetic variations of KIR-2DL1, 3DL1, and 3DS1 with their ligand genes (HLA-C2, HLA-Bw4/6, and Bw4, respectively) had effects on the risk of GB in Korean patients. The frequency of KIR-2DL1 with HLA-C2 (OR 2.05, CI 1.19-3.52, = 0.009), the frequency of KIR-3DL1 without HLA-Bw4 (80I) (OR 8.36, CI 4.06-17.18, < 0.001), and the frequency of KIR-3DL1 with Bw6 (OR 4.54, CI 2.55-8.09, < 0.001) in the GB group were higher than in the control group. In addition, the frequency of KIR-2DL1 without HLA-C2 (OR 0.44, CI 0.26-0.75, = 0.003), the frequency of KIR-3DL1 with HLA-Bw4 (80T) (OR 0.13, CI 0.06-0.27, < 0.001), the frequency of KIR-3DL1 without Bw6 (OR 0.27, CI 0.15-0.49, < 0.001), and the frequency of KIR-3DS1 with Bw4 (80I) (OR 0.03, CI 0.00-0.50, < 0.001) in the GB group were lower than in the control group.

CONCLUSIONS

This study suggests that genetic variations of KIRs and their ligand genes may affect GB development in the Korean population. Further investigations are needed to demonstrate the different immune responses for GB cells according to genetic variations of KIR genes and their ligand genes.

摘要

目的

自然杀伤（NK）细胞对癌细胞的免疫反应因患者而异。杀伤细胞免疫球蛋白样受体（KIR）是参与调节NK细胞杀伤癌细胞活性的一些主要受体，具有显著的基因变异。大量研究表明，KIR基因的基因变异与各种癌症类型的发生风险或预后之间存在潜在关联。然而，KIR基因的基因变异与胶质母细胞瘤（GB）之间的关联仍不确定。我们试图评估KIR及其配体基因的基因变异与韩国人患GB风险之间的关联。

方法

进行了一项病例对照研究，以确定KIR基因以及人类白细胞抗原（HLA）的A、B和C类对于GB的优势比（OR）。GB组由我们机构77例新诊断的异柠檬酸脱氢酶（IDH）野生型GB患者组成，对照组由200名健康韩国志愿者组成。

结果

GB组和对照组之间KIR基因和KIR单倍型的频率没有显著差异。KIR-2DL1、3DL1和3DS1与其配体基因（分别为HLA-C2、HLA-Bw4/6和Bw4）的基因变异对韩国患者患GB的风险有影响。GB组中KIR-2DL1与HLA-C2的频率（OR 2.05，CI 1.19 - 3.52，P = 0.009）、无HLA-Bw4（80I）的KIR-3DL1的频率（OR 8.36，CI 4.06 - 17.18，P < 0.001）以及有Bw6的KIR-3DL1的频率（OR 4.54，CI 2.55 - 8.09，P < 0.001）高于对照组。此外，GB组中无HLA-C2的KIR-2DL1的频率（OR 0.44，CI 0.26 - 0.75，P = 0.003）、有HLA-Bw（80T）的KIR-3DL1的频率（OR 0.13，CI 0.06 - 0.27，P < 0.001）、无Bw6的KIR-3DL1的频率（OR 0.27，CI 0.15 - 0.49，P < 0.001）以及有Bw4（80I）的KIR-3DS1的频率（OR 0.03，CI 0.00 - 0.50，P < 0.001）低于对照组。