Graft-versus-host Disease (GVHD) is the main cause of morbidity and mortality after allogeneic hematopoietic
stem cell transplantation (alloHSCT). In spite of immune-suppressive prophylaxis, most survivors suffer from
acute and chronic GVHD (aGVHD and cGVHD). The outcome of alloHSCT may be affected by the presence of
single nucleotide polymorphism (SNP) in non-HLA genes including those involved in innate immune responses.
This study aimed to evaluate the impact of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and caspase recruitment
domain 15 (NOD2/CARD15) gene polymorphisms on the incidence and severity of aGVHD and cGVHD following
alloHSCT. A structured literature review was carried out using various keywords and MESH terms such as
stem cell transplantation, allogenic haematopoietic stem cell transplantation, GVHD, and non-HLA gene
polymorphism, in PubMed, Google Scholar and Cochrane Database. A total of 8 studies that met inclusion
criteria (English publications from 2006 to 2017) were included. Ten SNPs in CTLA-4 gene and three SNPs in
NOD2/CARD15 gene were tested in patients with underlying haematological malignancies. Four studies tested
the SNPs of CTLA-4 gene and two were found to have an association with CTLA-4 SNPs (rs3087243, rs231775)
and increased incidence of aGVHD. The other four studies tested the SNPs of NOD2/CARD15 gene and one
found an association between SNP13 and increased incidence of aGVHD. None of these eight studies found
any effect on severity of GVHD. In conclusion, two SNPs in CTLA-4 and one SNP in NOD2/CARD15 increased
the incidence of aGVHD but not its severity. The higher incidence of aGVHD in studies with larger sample size
could support the impact of SNPs in the outcome of alloHSCT. However, due to the heterogeneity of studies in
regard to the age of patients and donor, and conditioning regimen, it is difficult to draw a definite conclusion.