Institute of Medicine, Chung Shan Medical University, and Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan.
Clin Chim Acta. 2011 May 12;412(11-12):958-62. doi: 10.1016/j.cca.2011.01.031. Epub 2011 Feb 2.
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.
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.
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.
IL-23R polymorphism may have a potential immuno-modulating role in long-term allograft outcome.
白细胞介素 23 受体 (IL-23R) 在多种自身免疫过程的发病机制中发挥作用。同种异体移植物结局与 IL-23R 变异基因型之间的关系以前尚未报道。因此，我们研究了这种遗传多态性与肾移植结局之间的关系。
这是一项观察性队列研究，共纳入 422 名肾移植受者 (RTR)。采用聚合酶链反应-限制性片段长度多态性检测 IL-23R 遗传多态性。我们使用包含血清肌酐 (SCr) 加倍、移植物失功和死亡的复合终点作为主要结局。次要结局包括经活检证实的急性排斥反应 (BPAR)、经活检证实的间质纤维化/肾小管萎缩 (IF/TA) 和单个主要结局。比较了不同 IL-23R 基因型和等位基因之间发生主要和次要结局的风险。
在平均 79.3±28.8 个月的随访中，IL-23R 基因型 AA 组的 26 例和 IL-23R 基因型 AC/CC 组的 32 例患者达到主要结局 (p=0.061)。与携带 IL-23R AA 基因型和 A 等位基因的 RTR 相比，携带 IL-23R AC/CC 基因型 (aHR 1.78；95%CI. 1.01-3.12；p=0.046) 和 C 等位基因 (aHR 1.48；95%CI. 0.96-2.28；p=0.075) 的 RTR 发生主要结局的风险更高。此外，与携带 IL-23R AA 基因型和 A 等位基因的 RTR 相比，携带 IL-23R AC/CC 基因型和 C 等位基因的 RTR 发生经活检证实的 IF/TA(p=0.012；p=0.012)和 SCr 加倍(p=0.024；p=0.042)的风险更高。IL-23R 基因型和等位基因之间的 BPAR、移植物失功和死亡风险无差异。
IL-23R 多态性可能在同种异体移植物长期结局中具有潜在的免疫调节作用。
