Objectives The effects of NOD2 single nucleotide polymorphisms (SNPs) on Grade III-IV acute graft-versus-host disease (aGVHD) risk are somewhat contradictory in different studies. The aim of the meta-analysis was to clarify the effects of NOD2 SNPs on the incidence of Grade III-IV aGVHD. Methods We searched PubMed, EMBASE, Web of SCIENCE, WanFang and Chinese National Knowledge Infrastructure (CNKI) databases to collect eligible publications. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between NOD2 polymorphisms and Grade III-IV aGVHD risk. Results A total of nine studies from eight publications met the inclusion criteria and were included in this meta-analysis. Patient NOD2 SNPs were not associated with aGVHD risk. A tendency of higher risk to develop Grade III-IV aGVHD was found in patients with pairs NOD2 SNPs. Subgroup analyses showed that pairs NOD2 SNPs were associated with Grade III-IV aGVHD in the Caucasian population and in identical sibling donors (IS), but not in matched unrelated donors (MUD). In patients who received hematopoietic stem cell transplantation (HSCT) with T-cell depletion and gut decontamination, there was still an association between pairs NOD2 SNPs and Grade III-IV aGVHD risk. Conclusions Our meta-analysis suggests that pairs NOD2 SNPs, not patient NOD2 SNPs, may be associated with Grade III-IV aGVHD risk, especially in the Caucasian population. It is also indicated that in pairs NOD2 polymorphisms group, patients who receive HSCT from IS may experience higher risk of Grade III-IV aGVHD.
Keywords: Acute graft-versus-host disease; Meta-analysis; NOD2; Risk; Single nucleotide polymorphisms.