A meta-analysis of the effects of interleukin-10 promoter gene polymorphisms on acute graft-versus-host disease susceptibility

Purpose: The interleukin-10 (IL-10) is an important immunomodulatory cytokine that regulates the effect of other inflammatory mediators in many aspects of immune responses. IL-10 promoter gene polymorphic features have been documented to contribute to the susceptibility of acute graft-versus-host disease(aGVHD). However, results of previous studies are inconsistent and inconclusive. A meta-analysis was performed to evaluate the association between the IL-10 promoter gene polymorphisms in allogeneic hematopoietic stem cell transplantation (alloHSCT) patients and donors on the risk of aGVHD.

Methods: Up to April 2012, databases including MEDLINE, EMBASE and Cochrane Library were searched to access the relevant genetic association studies. A total of 22 studies that referred IL-10 promoter gene polymorphisms on aGVHD susceptibility were identified. The effect of the IL-10 genetic polymorphisms on aGVHD risk (grades I-IV, II-IV, and III-IV) were estimated from odds ratios (OR) with 95% confidence intervals (CI) for the dominant genetic model and recessive model, respectively. 

Results: IL-10 -819 CC genotype was associated with the increased aGVHD risk when compared with CT+TT genotype (grade I-IV: OR, 2.722, 95% CI, 1.360-5.450; grade II-IV: OR, 2.130, 95% CI, 1.322-3.430). Furthermore, patients with IL-10 -592 C genotype had an increased risk of grade II-IV aGVHD (CC vs. A: OR, 1.999, 95% CI, 1.230-3.250) and grade III-IV aGVHD (CC vs. A: OR,  1.276, 95% CI, 1.067-1.526; C vs. AA: OR, 1.419, 95% CI, 1.001-2.012; CC vs. AA: OR, 1.534, 95% CI, 1.076-2.185; C vs. A: OR, 1.180, 95% CI, 1.000-1.392). Patients who received grafts from donors with the IL-10 C allele experienced less frequent grade III-IV aGVHD (OR, 0.711, 95% CI, 0.508-0.996). 

Conclusion: This meta-analysis suggests that the -819C/T and -592C/A polymorphisms of IL-10 gene could be a risk factor for aGVHD in allo-HSCT patients. Moreover, our meta-analysis confirms the linkage disequilibrium between two single nucleotide polymorphisms (SNPs) as identified in other previous studies.