Influence of interleukin-18 polymorphisms on kidney transplantation outcomes: A meta-analysis

Abstract

Aim: Allograft survival post-kidney transplantation (KT) are in large part attributed to genetics, which render the recipient susceptible or protected from allograft rejection. KT studies involving single nucleotide polymorphisms (SNPs) have reported the association of interleukin-18 (IL-18) with KT and its role in allograft rejection. However, the reported outcomes been inconsistent, prompting a meta-analysis to obtain more precise estimates. Methods: We posed two hypotheses about the IL-18 SNPs: their association with KT (H1), and increase or decrease in the risks of allograft rejection (H2). Using standard genetic models, we estimated odds ratios [ORs] and 95% confidence intervals by comparing the IL-18 genotypes between two groups: (i) patients and controls for H1 (GD: genotype distribution analysis); (ii) rejectors and non- rejectors for H2 (allograft analysis). Multiple comparisons were corrected with the Holm-Bonferroni (HB) test. Subgrouping was ethnicity-based (Asians and Caucasians). Heterogeneity was outlier-treated and robustness of outcomes was sensitivity-treated. Results: This meta-analysis generated eight significant outcomes, which HB filtered into four core outcomes, found in the dominant/codominant models. Two of the four were in GD, indicating associations of the IL-18 SNPs with KT (ORs 1.34 to 1.39, 95% CIs 1.13-1.70, PHB = .0007-.004). The other two were in allograft analysis indicating reduced risk with HB P-values of .03 for overall (OR 0.74, 95% CI 0.56-0.93) and Asian (OR 0.70, 95% CI 0.53-0.92). In contrast to the protected Asian subgroup, Caucasians showed non-significant increased risk (OR 1.20. 95% CI .82-1.75, Pa = .35). Sensitivity treatment conferred robustness to all the core outcomes. Conclusions: Overall association of IL-18 SNPs with KT was significant (up to 1.4-fold) and Asians KT recipients were protected (up to 30%). Enabled by outlier treatment, these findings were supported by non-heterogeneity and robustness. More studies may confirm or modify our findings.