Role of non-HLA gene polymorphisms in graft-versus-host disease.

A large number of reports have associated various non-HLA gene polymorphisms with the risk and severity of graft-versus-host disease (GVHD). To date, candidate gene studies and genome-wide association studies have been performed to investigate such non-HLA gene polymorphisms in relation to GVHD. Candidate gene studies are hypothesis-driven and cost-effective, whereas genome-wide association studies have the potential to discover new gene polymorphisms, including possible biomarkers and therapeutic targets. Some gene polymorphisms have the potential to affect protein function or gene expression, or to encode minor histocompatibility antigens. Non-HLA genotyping for genes influencing GVHD prior to transplantation should provide useful information that will facilitate choosing the donor, type of graft, conditioning treatment, and GVHD prophylaxis. However, attention should be paid to the need for validation studies and ethical issues.