Need for the clarification of data in a recent meta-analysis about cytokine gene polymorphisms and acute liver graft rejection

Abstract

We read with great interest the article entitled “Cytokine Gene Polymorphisms and Acute Liver Graft Rejection: A Meta-Analysis,”1 which was published in Liver Transplantation in 2005. The results suggest that the interleukin-10 (IL-10) polymorphism at position −1082 has been identified as a genetic risk factor for acute liver graft rejection: liver transplant recipients carrying the IL-10-1082 A allele displayed a lower rejection rate [common odds ratio (OR) = 0.6, 95% confidence interval (CI) = 0.4-0.9]. Nevertheless, some methodological issues need to be addressed with respect to the data provided in this meta-analysis by Warlé et al.1 First, the data reported by Warlé et al. for the study by Bathgate et al.2 do not seem to be in line with the data actually provided by Bathgate et al. Warlé et al. report that the incidence of acute rejection for individuals with the IL-10-1082 GG genotype was 42% (16/38), whereas the incidence was 58% (22/38) in Bathgate et al.'s study. Also, the data reported by Warlé et al. for the study by Jonsson et al.3 are not consistent with the data provided by Jonsson et al. Warlé et al. report that the rates of acute rejection for IL-10-1082 AA, IL-10-1082 AG, and IL-10-1082 GG genotype carriers were 25% (7/28), 27% (16/60), and 42% (14/33), respectively; however, the reported rates of acute rejection for individuals with the AA, AG, and GG genotypes were for the IL-10 polymorphism at position 1097 (ie, not at position −1082). Therefore, the study performed by Jonsson et al. should be excluded when studies of the IL-10-1082 G/A polymorphism and the risk of acute rejection are being pooled. When we excluded Jonsson et al.'s study and corrected the data for Bathgate et al.'s study, the pooled OR for the A allele versus the G allele was 0.76 (95% CI = 0.56-1.03) in a fixed effect model and 0.79 (95% CI = 0.49-1.28) in a random effect model. The results suggest that the IL-10-1082 G/A polymorphism is not associated with the risk of acute rejection in liver transplant recipients. We updated this analysis with a literature search (the last update was performed on March 1, 2011). Three additional studies4-6 were found for the IL-10-1082 G/A polymorphism and acute rejection in liver transplant recipients. When we included the 3 studies, the pooled OR for the A allele versus the G allele was 0.79 (95% CI = 0.60-1.05) in a fixed effect model and 0.82 (95% CI = 0.58-1.17) in a random effect model. The results still suggest that the IL-10-1082 G/A polymorphism is not associated with the risk of acute rejection in liver transplant recipients. Thus, these findings may imply that a role of the IL-10-1082 polymorphism in human liver graft rejection is not entirely credible. It would be helpful if the authors, taking this into account, were to provide a new, more accurate estimation of the pooled OR. Fei Liu M.D.*, Yonggang Wei M.D.*, Bo Li M.D.*, Lvnan Yan M.D.*, * Department of Liver and Vascular Surgery West China Hospital, Sichuan University Chengdu, Sichuan Province, China.