Influence of Interferon Gamma +874 T>A (rs2430561) Polymorphism on Renal Allograft Rejection: A Meta-analysis.

Background: Reported associations of the interferon gamma (IFNG) +874T/A (rs2430561) polymorphism with post-kidney transplantation allograft rejection (AR) have been inconsistent, prompting a meta-analysis to obtain more precise estimates.

Methods: Eighteen articles (22 studies) were included in the meta-analysis. Operating on the hypothesis that IFNG rs2430561 either increases or reduces AR risk, we used a genetic model-free approach to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Subgrouping was based on ethnicity (white, Middle Eastern, black, and mixed) and rejection type (ACR: acute rejection and CHR: chronic rejection). Quality of the associative effects was assessed with sensitivity treatment and test for publication bias.

Results: The overall analysis in the dominant model indicated increased risk (OR = 1.26; P = .02) was validated in the ACR subgroup (OR = 1.29; P = .01), which contrasted with the CHR subgroup, with a nonsignificant effect indicating reduced risk (OR = 0.83; P = .68). Only the black subgroup showed significant increased risk (OR = 2.87; P = .04), but the association was tenuous on account of low sample size (n = 2) and imprecise effect (95% CI, 1.07-7.73).

Conclusions: Increased risk associations (overall and ACR) of IFNG rs2430561 with AR is significant, robust, statistically powered, and lacking bias. Contrasting ACR (1.3-fold increased risk) and CHR (7% protective) effects may be clinically relevant in the genetics of renal transplantation.