Association between interleukin 23 receptor polymorphism and kidney transplant outcomes: a 10-year Taiwan cohort study

Abstract

Objective: Interleukin 23 receptor (IL-23R) plays a role in the pathogenesis of multiple autoimmune processes. The relationship between allograft outcomes and the IL-23Rvariant genotypes has not been reported on previously. Therefore, we examined the relationship between this genetic polymorphism and kidney transplant outcomes.

Methods: This is an observational cohort study and 422 renal transplant recipients (RTRs) were enrolled. Polymerase chain reaction-restriction fragment length polymorphism was used for the measurement of IL-23R genetic polymorphisms. We used a composite end-point incorporating serum creatinine (SCr) doubling, graft failure and death as the primary outcome. Secondary outcomes included biopsy-proven acute rejection (BPAR), biopsy-proven interstitial fibrosis/tubular atrophy (IF/TA) and individual primary outcome. The risks of developing primary and secondary outcomes were compared between the different IL-23R genotypes and alleles.

Results: With a mean follow-up of 79.3±28.8 months, 26 patients in the IL-23R genotype AA group and 32 patients in the IL-23R genotype AC/CC group reached the primary outcome (p=0.061). RTRs who carried the IL-23R AC/CC genotype (aHR 1.78; 95% CI. 1.01-3.12; p=0.046) and C allele (aHR 1.48; 95% CI. 0.96-2.28; p=0.075) had a higher risk of developing primary outcome as compared to those with IL-23R AA genotype and A allele, respectively. Moreover, RTRs who carried the IL-23R AC/CC genotype and C allele had a higher risk of developing biopsy-proven IF/TA (p=0.012; p=0.012) and SCr doubling (p=0.024; p=0.042) as compared to those with IL-23R AA genotype and A allele, respectively. The risk of BPAR, graft failure and death between the IL-23R genotypes and alleles were comparable.

Conclusion: IL-23R polymorphism may have a potential immuno-modulating role in long-term allograft outcome.