Toggle Main Menu Toggle Search

Open Access padlockePrints

Genetic Association of Hematopoietic Stem Cell Transplantation Outcome beyond Histocompatibility Genes

Lookup NU author(s): Rihab Gam, Pranali Shah, Dr Rachel Crossland, Jean Norden, Professor Anne Dickinson

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2017 Gam, Shah, Crossland, Norden,Dickinson and Dressel. The outcome of hematopoietic stem cell transplantation (HSCT) is controlled by genetic factors among which the leukocyte antigen human leukocyte antigen (HLA) matching is most important. In addition, minor histocompatibility antigens and non-HLA gene polymorphisms in genes controlling immune responses are known to contribute to the risks associated with HSCT. Besides single-nucleotide polymorphisms (SNPs) in protein coding genes, SNPs in regulatory elements such as microRNAs (miRNAs) contribute to these genetic risks. However, genetic risks require for their realization the expression of the respective gene or miRNA. Thus, gene and miRNA expression studies may help to identify genes and SNPs that indeed affect the outcome of HSCT. In this review, we summarize gene expression profiling studies that were performed in recent years in both patients and animal models to identify genes regulated during HSCT. We discuss SNP-mRNA-miRNA regulatory networks and their contribution to the risks associated with HSCT in specific examples, including forkheadbox protein 3 and regulatory T cells, the role of the miR-155 and miR-146a regulatory network for graft-versus-host disease, and the function of MICA and its receptor NKG2D for the outcome of HSCT. These examples demonstrate how SNPs affect expression or function of proteins that modulate the alloimmune response and influence the outcome of HSCT. Specific miRNAs targeting these genes and directly affecting expression of mRNAs are identified. It might be valuable in the future to determine SNPs and to analyze miRNA and mRNA expression in parallel in cohorts of HSCT patients to further elucidate genetic risks of HSCT.


Publication metadata

Author(s): Gam R, Shah P, Crossland RE, Norden J, Dickinson AM, Dressel R

Publication type: Review

Publication status: Published

Journal: Frontiers in Immunology

Year: 2017

Volume: 8

Online publication date: 03/04/2017

Acceptance date: 16/03/2017

ISSN (electronic): 1664-3224

Publisher: Frontiers Research Foundation

URL: https://doi.org/10.3389/fimmu.2017.00380

DOI: 10.3389/fimmu.2017.00380


Actions

Find at Newcastle University icon    Link to this publication


Share