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

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

doi:10.3390/jcm12144780

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

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

Authors

Haeyoun Choi^{1

2}, In-Cheol Baek², Soon A Park³, Jae-Sung Park⁴, Sin-Soo Jeun⁴, Tai-Gyu Kim^{1

2}, Stephen Ahn⁴

Affiliations

¹ Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
² Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
³ Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
⁴ Department of Neurosurgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.

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, p = 0.009), the frequency of KIR-3DL1 without HLA-Bw4 (80I) (OR 8.36, CI 4.06-17.18, p < 0.001), and the frequency of KIR-3DL1 with Bw6 (OR 4.54, CI 2.55-8.09, p < 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, p = 0.003), the frequency of KIR-3DL1 with HLA-Bw4 (80T) (OR 0.13, CI 0.06-0.27, p < 0.001), the frequency of KIR-3DL1 without Bw6 (OR 0.27, CI 0.15-0.49, p < 0.001), and the frequency of KIR-3DS1 with Bw4 (80I) (OR 0.03, CI 0.00-0.50, p < 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.

Keywords: KIR; Koreans; glioblastoma; immunogenetics; polymorphism.

Grants and funding

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF- 2020R1I1A1A01072972 and 2021R1I1A1A01055575) and by the Research Fund of Seoul St. Mary’s Hospital, The Catholic University of Korea (ZC22CISI0705). The funders had no role in this study.