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中国汉族人群中与移植后糖尿病相关的多个基因变异体。

Multiple genetic variants associated with posttransplantation diabetes mellitus in Chinese Han populations.

作者信息

Chen Jie, Li Lixin, An Yunfei, Zhang Junlong, Liao Yun, Li Yi, Wang Lanlan

机构信息

Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, China.

出版信息

J Clin Lab Anal. 2018 Mar;32(3). doi: 10.1002/jcla.22308. Epub 2017 Aug 23.

Abstract

OBJECTIVES

Posttransplantation diabetes mellitus (PTDM) is a major complication after solid organ transplantation. This study is to investigate the association of nine genetic variant factors and PTDM in Chinese Han patients.

METHODS

HLA-DP (rs3077, rs9277535), HLA-DQ (rs7453920), signal transducer and activator of transcription 4 (STAT4) (rs7574865), IL-28B (rs12979860, rs8099917, and rs12980275), and IL-18 (rs1946518 and rs187238) were investigated in 260 liver transplant recipients (PTDM vs non-PTDM) by high-resolution melting curve analysis. Serum interleukin (IL)-1β, IL-6, IL-8, IL-17, interferon-γ, inducible protein-10, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1b were analyzed by a Bio-Plex suspension array system (Bio-Plex Multiplex Immunoassays, Bio-Rad, Hercules, CA, USA).

RESULTS

Signal transducer and activator of transcription 4 (rs7574865) T allele and IL-18 (rs1946518) A allele increase the risk for insulin resistance and PTDM.

CONCLUSIONS

Recipients with STAT4 (rs7574865) T allele are associated with an increased concentration of IL-1β, interferon-γ, monocyte chemoattractant protein, and macrophage inflammatory protein-1b. The genetic variants of STAT4 (rs7574865) and IL-18 (rs1946518) may be new important markers for PTDM.

摘要

目的

移植后糖尿病(PTDM)是实体器官移植后的一种主要并发症。本研究旨在调查9种基因变异因素与中国汉族患者PTDM的相关性。

方法

采用高分辨率熔解曲线分析技术,对260例肝移植受者(PTDM组与非PTDM组)的HLA-DP(rs3077、rs9277535)、HLA-DQ(rs7453920)、信号转导和转录激活因子4(STAT4)(rs7574865)、IL-28B(rs12979860、rs8099917和rs12980275)以及IL-18(rs1946518和rs187238)进行检测。采用Bio-Plex悬浮阵列系统(Bio-Plex多重免疫分析,美国伯乐公司,加利福尼亚州赫拉克勒斯市)分析血清白细胞介素(IL)-1β、IL-6、IL-8、IL-17、干扰素-γ、诱导蛋白-10、单核细胞趋化蛋白-1和巨噬细胞炎性蛋白-1b。

结果

信号转导和转录激活因子4(rs7574865)T等位基因和IL-18(rs1946518)A等位基因增加胰岛素抵抗和PTDM的风险。

结论

携带STAT4(rs7574865)T等位基因的受者血清IL-1β、干扰素-γ、单核细胞趋化蛋白和巨噬细胞炎性蛋白-1b浓度升高。STAT4(rs7574865)和IL-18(rs1946518)的基因变异可能是PTDM新的重要标志物。

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