The association between genetic variants at 3'-UTR and 5'-URR of HLA-G gene and the clinical outcomes of patients with leukemia receiving hematopoietic stem cell transplantation

Ding-Ping Chen; Po-Nan Wang; Ai-Ling Hour; Wei-Tzu Lin; Fang-Ping Hsu; Wei-Ting Wang; Ching-Ping Tseng

doi:10.3389/fimmu.2023.1093514

The association between genetic variants at 3'-UTR and 5'-URR of HLA-G gene and the clinical outcomes of patients with leukemia receiving hematopoietic stem cell transplantation

Front Immunol. 2023 Feb 23:14:1093514. doi: 10.3389/fimmu.2023.1093514. eCollection 2023.

Authors

Ding-Ping Chen^{1

2}, Po-Nan Wang³, Ai-Ling Hour⁴, Wei-Tzu Lin¹, Fang-Ping Hsu¹, Wei-Ting Wang¹, Ching-Ping Tseng^{1

2

5}

Affiliations

¹ Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
² Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
³ Division of Hematology-Oncology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁴ Department of Life Science, Fu Jen Catholic University, New Taipei City, Taiwan.
⁵ Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.

Abstract

In addition to the classical human leukocyte antigen (HLA) genes, the outcomes of post-hematopoietic stem cell transplantation (HSCT) are associated with human leukocyte antigen (HLA)-related genes and non-HLA genes involved in immune regulation. HLA-G gene plays an important role in immune tolerance, assisting immune escape of tumor cells, and decrease of transplant rejection. In this study, we explored the association of genetic variants at the 3'-untranslated region (3'-UTR) and 5'-upstream regulatory region (5'-URR) of HLA-G gene with the adverse outcomes of patients with leukemia receiving HSCT. The genomic DNAs of 164 patients who had acute leukemia and received HSCT were collected for analysis. Nine single nucleotide polymorphisms (SNPs) and six haplotypes in the 3'-UTR and 27 SNPs and 6 haplotypes in the 5'-URR were selected to investigate their relationship with the development of adverse outcomes for patients receiving HSCT, including mortality, relapse, and graft-versus-host disease. Our results revealed that two SNPs (rs371194629 and rs9380142) and one haplotype (UTR-3) located in the 3'-UTR and two SNPs (rs3823321 and rs1736934) and one haplotype (G0104a) located in the 5'-URR of HLA-G were associated with the occurrence of chronic GVHD or development of any forms of GVHD. No SNP was found to associate with the occurrence of mortality and relapse for patients receiving HSCT. These SNPs and haplotypes may play important roles in regulating immune tolerance of allografts post-HSCT that can be used to predict the risk of poor outcomes after receiving HSCT and giving preventive treatment to patients on time.

Keywords: graft versus host disease (GVHD); haplotype; hematopoietic stem cell transplantation (HSCT); human leukocyte antigen-G (HLA-G); single nucleotide polymorphism (SNP).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Graft vs Host Disease*
HLA-G Antigens / genetics
Hematopoietic Stem Cell Transplantation* / adverse effects
Histocompatibility Antigens Class II
Humans
Leukemia, Myeloid, Acute* / genetics
Recurrence

Substances

HLA-G Antigens
Histocompatibility Antigens Class II

Grants and funding

This study was supported by grants to D-PC from the Chang Gung Memorial Hospital (CMRPG3L0771-2), and to C-PT from the Chang Gung Memorial Hospital (CMRPD1M0071-2, CMRPD1L0281-2, CORPD1K0031, and BMRP466) and the Ministry of Science and Technology (109-2320-B-182-031-MY3). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.