A Meta-Analysis of the Effects of Interleukin-6 −174 G>C Genetic Polymorphism on Acute Graft-Versus-Host Disease Susceptibility

BackgroundThe interleukin-6 (IL-6) −174 G>C genetic polymorphism has been implicated to play an important role in acute graft-versus-host disease (aGVHD). However, previous studies have yielded inconclusive results as to its role in patient susceptibility to aGVHD, and no study to date has systematically analyzed this polymorphism.ObjectiveA meta-analysis of the published evidence was conducted to estimate the true effect of the IL-6 −174 G>C genetic polymorphism in allogeneic hematopoietic stem cell transplantation (alloHSCT) patients and donors on the risk of aGVHD.MethodsSeven cohort studies, comprising 1287 recipient and donor pairs, were included after eliminating 62 studies that met the following exclusion criteria: irrelevant studies other than cohort studies, without sufficient data, and with overlapping data. Although interstudy heterogeneity existed, most studies were conducted in the United States or Europe and included adult patients with hematologic disease who received alloHSCT from human leukocyte antigen–matched or identical sibling donors. The effect of the polymorphism on aGVHD risk (grades I-IV, II-IV, and III-IV) was estimated from odds ratios with 95% confidence intervals for the dominant genetic model and recessive model, respectively.ResultsPatients who received grafts from donors with the IL-6 G allele experienced more frequent grade I-IV aGVHD (odds ratio = 3.304 [95% confidence interval, 1.456-7.494]) and grade II-IV aGVHD (odds ratio = 1.738 [95% CI, 1.006 - 3.001]).ConclusionsTo our knowledge, this is the first meta-analysis to evaluate the relation between a non–human leukocyte antigen gene polymorphism and the risk of aGVHD. Our meta-analysis combined the results of several studies and demonstrated that the donor IL-6 G allele is associated with an increased risk of grades I-IV and II-IV aGVHD.