Association of Genetic Polymorphisms of Interleukins With New-Onset Diabetes After Transplantation in Renal Transplantation
Association of Genetic Polymorphisms of Interleukins With New-Onset Diabetes After Transplantation in Renal Transplantation
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DOI：
10.1097/tp.0b013e3182497534
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发表时间：
2012-05-15
期刊：
影响因子：
6.2
通讯作者：
Kim, Yeong Hoon
中科院分区：
文献类型：
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作者：
Kim, Yang Gyun;Ihm, Chun-Gyoo;Kim, Yeong Hoon
背景。移植后新发糖尿病（NODAT）是一种严重的代谢并发症。尽管 A 细胞功能障碍被认为是 NODAT 发生的主要因素，但确切的发病机制尚未确定。尽管多种细胞因子被认为与糖尿病中胰岛β细胞的炎症有关，但很少有研究检查NODAT中的A细胞功能障碍。因此，我们检测了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，这可能与肾移植后A细胞功能障碍有关。 方法。共有 306 名没有糖尿病史的肾移植受者被纳入研究。我们分析了 NODAT 发育与 IL 或其受体的 10 个基因内的一组 18 个 SNP 之间的关联。结果。就等位基因频率而言，NODAT 患者中 rs2069763*T (IL-2)、rs1494558*A 和 rs2172749*C (IL-7R) 以及 rs4819554*A (IL-17R) 显着较高。调整年龄、性别和他克莫司使用后，18 名患者中的 11 个 SNP (61.1%) 与 NODAT 发育显着相关。它们包括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)。结论。数据表明，胰岛 A 细胞的炎症可能在肾移植受者 NODAT 的发病机制中发挥至关重要的作用。特别是，最近报道与 1 型糖尿病相关的 IL-7R、IL-17E、IL-17R 和 IL-17RB 的显着变异可能与肾移植受者 NODAT 的发病机制有关。
Background. New-onset diabetes after transplantation (NODAT) is a serious metabolic complication. Although A-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 A-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 A-cell dysfunction after kidney transplantation.Methods. 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.Results. In terms of allele frequencies, rs2069763*T (IL-2), rs1494558*A and rs2172749*C (IL-7R), and rs4819554*A (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).Conclusions. The data suggest that inflammation of islet A 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.