Association between single nucleotide polymorphisms of tumor necrosis factor gene and grade II-IV acute GvHD: a systematic review and meta-analysis.

Acute GvHD (aGvHD) complicates up to 50% of allogeneic hematopoietic cell transplants and pre-transplant estimation of its risk can guide prophylaxis, monitoring and early intervention strategies. Inspired by the role of tumor necrosis factor alpha (TNFα) in the pathogenesis of aGvHD and the inconsistency of the association studies exploring single nucleotide polymorphisms (SNPs) of the TNF gene, we conducted a systematic review and meta-analysis of the available reports using PubMed and EMBASE. Original human studies reporting on the association between recipient TNF SNPs and grade II-IV aGvHD in a format convertible to effect size and confidence interval were included. One of the two most widely investigated SNPs (rs361525G>A) was marginally associated with increased risk of grade II-IV aGvHD in random-effects meta-analysis of six studies (627 patients in total, risk ratio=1.29, 95% confidence interval=0.99-1.69, P=0.06). If this result is validated in a large cohort with uniform conditioning and GvHD prophylaxis, TNF rs361525G>A may become a useful tool for aGvHD risk estimation before the transplant.