Distinct NOD2 polymorphism status is associated with differential outcome in hematopoietic stem cell transplantation: results from a meta-analysis

Abstract

Objective: Susceptibility to Graft-Versus-Host Disease (GvHD) following Hematopoietic Stem Cell Transplantation (HSCT) has been linked to the NOD2 gene, but results have been so far conflicting among individual studies. The aim of this meta-analysis was to investigate NOD2 (nucleotide-binding oligomerisation domain containing 2) polymorphisms as possible susceptibility loci for GvHD as well as other life-threatening complications following HSCT. Methods: Available studies addressing a possible contribution of NOD2 polymorphisms to GvHD and complications following HSCT were identified through database searches. We analyzed the HSCT outcomes and any of the NOD2 polymorphisms in either donor or recipient. Pooled relative risks (RRs) and their 95 % CI were calculated to assess the strength of correlation. Results: NOD2 polymorphisms whether in recipient or donor, or recipient and donor-side transplant pairs, were significantly associated with severe GvHD (P = 0.004). However, only trends were observed in terms of the association between polymorphisms and decreasing mild GvHD, 1-year overall survival, disease-free survival, or increasing transplantation-related mortality and relapse (P > 0.05). NOD2 polymorphisms on the donor-side only were associated with higher risk of severe GvHD (P = 0.09), and the association was also observed in pairs where polymorphisms were carried by both the recipient and the donor (P = 0.002). Increased GvHD risk was not associated with polymorphisms in recipient-side only transplant pairs. Furthermore, the association was not attributable to any specific NOD2 genotype. Conclusions: NOD2 polymorphism confers the more negative outcomes following HSCT. Donor and both-side mutation in transplants could increase the risk of severe GvHD. NOD2 genotyping may therefore be of clinical value.

Risk Prediction Genetic Study of Non-HLA Gene NOD2 Three Polymorphisms in Acute Graft versus Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

“…In the present study, no significant association between donors/ recipients G908 SNP and aGVHD p=0.8. As well as donors / recipients R702W SNP and aGVHD p=0.8.Our results are consistent with Nguyen et al 26 & Tanabe et al 28 .Controversly, Van der et al 29 & Zhao et al 23 reported significant association. These conflicting results regarding G908R and R702W SNPs with our results may be due to first, the number of NOD2 genotypes analyzed were limited 3.1%, 1.6% compared to 7%, 8%, and may, therefore, ultimately reduce the power of analysis.…”

“…In this study no significant association between donor NOD2 1007fs SNP and aGVHD p=0.5.These results are consistent with other studies 25, 26 . In contrast, some studies show significant association between donor NOD2 1007fs SNP and aGVHD 8, 23 . This conflict may be attributed to ethnic variation / narrow scale study population.…”

“…These results were consistent with Gruhn et al 30 who reported no significant association between donor / recipients NOD2 SNPs and cGVHD. Zhao et al 23 also reported no significant association between cGVHD and NOD2 genotype in donor and recipient.…”