Division of Nephrology, School of Medicine, Kyung Hee University, Seoul, Korea.
Transplantation. 2012 May 15;93(9):900-7. doi: 10.1097/TP.0b013e3182497534.
New-onset diabetes after transplantation (NODAT) is a serious metabolic complication. Although β-cell dysfunction is considered the main contributing factor in the development of NODAT, the precise pathogenesis has not been identified. Although several cytokines have been suggested to be involved in the inflammation of islet beta cells in diabetes mellitus, only rarely have studies examined β-cell dysfunction in NODAT. Therefore, we examined the association between NODAT and 18 single nucleotide polymorphisms (SNPs) located within the 10 genes of interleukins (IL) or their receptors, which might be related with β-cell dysfunction after kidney transplantation.
A total of 306 renal transplants recipients were included without a history of diabetes. We analyzed the association between NODAT development and a panel of 18 SNPs within 10 genes of IL or their receptors.
In terms of allele frequencies, rs2069763T (IL-2), rs1494558A and rs2172749C (IL-7R), and rs4819554A (IL-17R) were significantly higher in patients with NODAT. Eleven SNPs among 18 (61.1%) were significantly associated with NODAT development after adjusting for age, sex, and tacrolimus usage. They include IL-1B (rs3136558), IL-2 (rs2069762), IL-4 (rs2243250, rs2070874), IL-7R (rs1494558, rs2172749), IL-17RE (rs1124053), IL-17R (rs2229151, rs4819554), and IL-17RB (rs1043261, rs1025689).
The data suggest that inflammation of islet β cells might play a crucial role in the pathogenesis of NODAT in renal transplantation recipients. In particular, significant variations of IL-7R, IL-17E, IL-17R, and IL-17RB, which was recently reported to be associated with type 1 diabetes mellitus, could be associated with the pathogenesis of NODAT in renal transplant recipients.
移植后新发糖尿病（NODAT）是一种严重的代谢并发症。虽然β细胞功能障碍被认为是 NODAT 发展的主要致病因素，但确切的发病机制尚未确定。尽管有几种细胞因子被认为与糖尿病胰岛β细胞炎症有关，但很少有研究检查 NODAT 中的β细胞功能障碍。因此，我们研究了 NODAT 与位于白细胞介素（IL）或其受体的 10 个基因内的 18 个单核苷酸多态性（SNP）之间的关联，这些 SNP 可能与肾移植后β细胞功能障碍有关。
共纳入 306 例无糖尿病病史的肾移植受者。我们分析了 NODAT 发展与白细胞介素或其受体 10 个基因内的 18 个 SNP 之间的关联。
在等位基因频率方面，NODAT 患者的 IL-2 中的 rs2069763T、IL-7R 中的 rs1494558A 和 rs2172749C 以及 IL-17R 中的 rs4819554A 明显更高。在调整年龄、性别和他克莫司使用后，18 个 SNP 中有 11 个（61.1%）与 NODAT 发展显著相关。包括 IL-1B(rs3136558)、IL-2(rs2069762)、IL-4(rs2243250、rs2070874)、IL-7R(rs1494558、rs2172749)、IL-17RE(rs1124053)、IL-17R(rs2229151、rs4819554)和 IL-17RB(rs1043261、rs1025689)。
数据表明，胰岛β细胞炎症可能在肾移植受者 NODAT 的发病机制中起关键作用。特别是最近报道与 1 型糖尿病相关的白细胞介素 7R、白细胞介素 17E、白细胞介素 17R 和白细胞介素 17RB 的显著变异，可能与肾移植受者 NODAT 的发病机制有关。
