title: The association between cytokine gene polymorphisms and graft rejection in liver transplantation: a systematic review and meta-analysis.
abstract: We investigated the contribution of polymorphisms in cytokine genes (TNFa-308, IL10-1082 and -592, TGFb1-c10 and c25, and IFNg+874) on the risk of graft rejection in liver transplantation. We performed a systematic review by identifying relevant studies and applied meta-analysis to pool gene effects. In total, 12 studies were eligible and included in the study. Data extraction and assessments for risk of bias were independently performed by two reviewers. Data for allele frequencies, allelic, and genotypic effects were pooled. Heterogeneity and publication bias were assessed. Pooled minor allele frequencies for TNFa-308, IL10-1082, TGFb1-c10, TGFb1-c25, IFNg+874, and IL10-592 were 0.140 (95% CI: 0.083, 0.198), 0.432 (95% CI: 0.392, 0.472), 0.387 (95% CI: 0.307, 0.467), 0.090 (95% CI: 0.056, 0.123), 0.460 (95% CI: 0.392, 0.528), and 0.224 (95% CI: 0.178, 0.269), respectively. OnlyTNFa-308 and IL10-1082 polymorphisms were significantly associated with graft rejection. Patients who carried minor homozygous genotypes for these two polymorphisms were at 3.5 and 1.69 times higher risk of graft rejections than patients who carried major homozygous genotypes. The estimated lambdas were 0.41 and 0.47, suggesting an additive mode of effect was most likely. However, we could not detect the associations of TGFb1at c10 and c25, INFg+874, and IL10-592 polymorphisms and graft rejection. In summary, our systematic review has demonstrated that TNFa-308 and IL10-1082 are potential risk factors of poor outcomes in liver transplantation. Future updated meta-analysis studies to confirm the power of these genotypes in association with allograft rejection are needed.
authors.affiliation: Section for Clinical Epidemiology and Biostatistics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. sasivimol.rat@mahidol.ac.th
authors.forename: Sasivimol
authors.initials: S
authors.lastname: Rattanasiri
authors.forename: D Olga
authors.initials: DO
authors.lastname: McDaniel
authors.forename: Mark
authors.initials: M
authors.lastname: McEvoy
authors.forename: Thunyarat
authors.initials: T
authors.lastname: Anothaisintawee
authors.forename: Abhasnee
authors.initials: A
authors.lastname: Sobhonslidsuk
authors.forename: John
authors.initials: J
authors.lastname: Attia
authors.forename: Ammarin
authors.initials: A
authors.lastname: Thakkinstian
mesh_terms: D016207:Cytokines / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology*; D006801:Humans; D016031:Liver Transplantation; D011110:Polymorphism, Genetic; D011183:Postoperative Complications / Q000276:immunology*; D012307:Risk Factors
chemical_list: D016207:Cytokines