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miR-146a多态性与糖尿病周围神经病变及临床疗效的相关性研究

Associations of miR-146a polymorphism with diabetic peripheral neuropathy and clinical effect

    摘要
  • 摘要:
      目的  探讨2型糖尿病(T2DM)患者miR-146a基因多态性与糖尿病周围神经病变(DPN)易感性和临床疗效的相关性。
      方法  选取524例T2DM患者作为研究对象，将299例单纯T2DM患者纳入单纯T2DM组, 225例T2DM合并DPN患者纳入DPN组。提取所有患者血液DNA并应用TaqMan探针法分析miR-146a基因多态性，DPN组患者均接受依帕司他和甲钴胺治疗，分析miR-146a基因多态性与DPN易感性及临床疗效的相关性。
      结果  DPN组患者糖尿病病程长于单纯T2DM组，空腹血糖(FPG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)和胰岛素抵抗指数(HOMA-IR)水平均高于单纯T2DM组，差异有统计学意义(P < 0.05); DPN组GG基因型分布频率高于单纯T2DM组, CG基因型分布频率低于T2DM组，差异有统计学意义(P < 0.05); 二分类Logistic回归分析显示，糖尿病病程、FPG、HbA1c、HOMA-IR和miR-146a基因分型均为T2DM患者发生DPN的独立影响因素(P < 0.05); GG基因型患者DPN易感性高于CC基因型患者，差异有统计学意义(P < 0.05); 治疗3个月后, DPN患者腓总神经、尺神经、胫神经和正中神经的运动和感觉神经传导速度高于治疗前，多伦多临床评分系统(TCSS)评分低于治疗前，差异有统计学意义(P < 0.05)。治疗3个月后, GG基因型DPN患者运动感觉神经传导速度低于CC基因型、CG基因型患者, TCSS评分高于CC基因型、CG基因型患者，差异有统计学意义(P < 0.05)。
      结论  miR-146a基因多态性与T2DM患者DNP易感性及临床疗效有关, GG基因型T2DM患者的DNP易感性较高且临床疗效较差。

     

    Abstract:
      Objective  To investigate the relationships between the miR-146a polymorphism and diabetic peripheral neuropathy (DPN), clinical efficacy of patients with type 2 diabetes mellitus (T2DM).
      Methods  A total of 524 patients with T2DM were enrolled, including 299 patients with simple diabetes mellitus (simple T2DM group) and 225 T2DM patients with DPN (DPN group). Blood DNA was extracted from all patients and polymorphisms in the miR-146a gene were analyzed using TaqMan probe. All patients with DPN were treated with epinostat and mecobalamin, and the associations between miR-146a gene polymorphisms and DPN of susceptibility, clinical efficacy were compared.
      Results  The duration of diabetes in the DPN group was longer than that in the simple T2DM group, fasting blood glucose(FPG), hemoglobin A1c (HbA1c), fasting insulin(FINS) and insulin resistance index(HOMA-IR) in the DPN group were significantly higher than those in the simple T2DM group (P < 0.05). The distribution frequency of GG genotype in the DPN group was higher than that in the simple T2DM group (P < 0.05), but the distribution frequency of CG genotype was lower than that in the simple T2DM group (P < 0.05). Binary Logistic regression analysis showed that the duration of diabetes mellitus, FPG, HbA1C, HOMA-IR and miR-146a genotypes were independent risk factors for DPN in T2DM patients (P < 0.05). The susceptibility of DPN in patients with GG genotype was significantly higher than that in patients with CC genotype (P < 0.05). After 3 months of treatment, the motor and sensory nerve conduction velocities of the peroneal, ulnar, tibial and median nerves were significantly increased (P < 0.05), and the Toronto Clinical Scoring System (TCSS) scores were significantly decreased (P < 0.05). After 3 months of treatment, motor sensory nerve conduction velocity in patients with GG genotype was significantly lower than that of CC or CG genotype patients (P < 0.05), TCSS score was significantly higher than that in patients with CC or CG genotype (P < 0.05).
      Conclusion  The gene polymorphism of miR-146a is associated with susceptibility and clinical outcome of DNP. In T2DM patients with GG genotype, the risk of DNP is higher and the clinical outcome is worse.

     

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