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Non-HLA genomics: does it have a role in predicting haematopoietic stem cell transplantation outcome?

Lookup NU author(s): Professor Anne Dickinson, Jean Norden


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Haematopoietic stem cell transplantation (HSCT) remains the only cure for many haematological neoplasms; however, the mortality rate remains high, at around 30-80%. Complications after HSCT include relapse, graft-versus-host disease, graft rejection and infection. High-resolution HLA matching has improved survival in HSCT over recent years; however, GVHD still remains a serious complication. Single nucleotide polymorphisms (SNPS) within genes that are involved with an individual's capability to mount an immune response to infectious pathogens, residual leukaemia, alloantigens or genes involved in drug metabolism have been studied for their association with HSCT outcome. Indeed, over the last 15years, several groups, including ourselves, have demonstrated that non-HLA gene polymorphisms can be predictive of HSCT outcome. Can genetic characteristics of the patient and donor be used in the future to tailor HSCT protocols and determine GVHD prophylaxis? This review summarizes some of the recent SNP association studies in HSCT and highlights some of the disparities therein, discussing the integral problems of performing genetic association studies on diseases with complex outcomes using heterogeneous cohorts. The review will comment on recent genomewide association studies (GWAS) and discuss their relevance in this field, and it will also comment on recent meta-analysis combining GWAS studies with other studies such as gene expression micro array data in the field of autoimmune disease and solid organ transplantation. It will mention possible novel candidate gene polymorphisms, for example SNPS in microRNAs. In addition, it will discuss some of the inherent problems associated with gene association studies including the GRIPs (genetic risk prediction studies) recommendations. In summary, this review will assess the usefulness of non-HLA genomic studies in HSCTwith regard to predicting outcome and modifying therapy.

Publication metadata

Author(s): Dickinson AM, Norden J

Publication type: Review

Publication status: Published

Journal: International Journal of Immunogenetics

Year: 2015

Volume: 42

Issue: 4

Pages: 229-238

Print publication date: 01/08/2015

Online publication date: 23/05/2015

Acceptance date: 31/03/2015

ISSN (print): 1744-3121

ISSN (electronic): 1744-313X



DOI: 10.1111/iji.12202