miR-146a rs2910164多态性对miR-146a表达的影响及与糖尿病周围神经病变的相关性研究

详细信息    查看全文 | 推荐本文 |

英文篇名：Influence of miR-146a rs2910164 on abnormal expression of miR-146a and its susceptibility to diabetic peripheral neuropathy 作者：王国凤 ; 尹冬 ; 徐宁 ; 惠媛 ; 韩冠军 ; 杨传慧 ; 闫永鑫 ; 梁程程 英文作者：WANG Guofeng;YIN Dong;XU Ning;YAN Yongxin;Department of Endocrinology,The Affiliated of Lianyungang Hospital of Xuzhou Medical University; 关键词：糖尿病 ; 2型 ; 糖尿病周围神经病变 ; 基因多态性 ; miR-146a ; rs2910164 英文关键词：Diabetes mellitus,type 2;;Diabetic peripheral neuropathy;;Genetic polymorphism;;miR-146a rs2910164 中文刊名：ZGTL 英文刊名：Chinese Journal of Diabetes 机构：徐州医科大学附属连云港医院内分泌科;徐州医科大学附属连云港医院普外科;徐州医科大学附属连云港医院呼吸内科; 出版日期：2019-02-20 出版单位：中国糖尿病杂志 年：2019 期：v.27 基金：连云港市卫生科技项目(局1402,201510) 语种：中文; 页：ZGTL201902005 页数：6 CN：02 ISSN：11-5449/R 分类号：28-33

摘要

目的探讨miR-146a rs2910164与糖尿病周围神经病变(DPN)易感性的相关性及其对miR-146a表达的影响。方法应用TaqMan探针法和实时荧光定量聚合酶反应,分别检测386例T2DM患者(T2DM组)、366例DPN患者(DPN组)及395名健康体检人群(NC组)miR-146a rs2910164基因多态性和miR-146a的表达水平。分析各组miR-146a rs2910164基因多态性,二分类Logistic回归分析DPN的影响因素。结果 miR-146a rs2910164位点等位基因G在NC组和T2DM组分别为56. 83%和55. 18%,GG、GC、CC基因型分别为31. 39%、50. 88%、17. 72%和30. 31%、49. 74%、19. 95%,差异均无统计学意义(P>0. 05);与NC组和T2DM组相比,DPN组G等位基因和GG基因型频率升高(P<0. 05);调整年龄、病程、HbA1c等因素后回归分析结果显示,与基因型CC相比,基因型GG的DPN患病风险较高[OR(95%CI)2. 34(1. 12～4. 82),P=0. 013];校正各种因素后,差异仍有统计学意义[OR(95%CI)2. 31(1. 02～4. 98),P=0. 023]。携带GG基因型的个体具有较高的SBP、FPG、HbA1c、UACR、HOMA-IR,以及较长的糖尿病病程和低水平miR-146a的表达量。二分类Logisitc回归分析结果显示,miR-146a rs2910164基因多态性、HbA1c、糖尿病病程是DPN的危险因素。结论 miR-146a rs2910164中基因型GG降低miR-146a表达水平,与糖尿病病程、HbA1c、HOMA-IR存在一定相关性,可能增加DPN的遗传易感性。
        Objective To explore the association between miR-146a rs2910164 and type 2 diabetic peripheral neuropathy and its influence on miR-146 a expression. Methods The polymorphism of rs2910164 and the expression level of miR-146 a were measured by TaqMan method and real-time RT-PCR respectively all the study subjects, including three groups: patients with type 2 diabetes(T2DM group, n =386), patients with type 2 diabetic peripheral neuropathy(DPN group, n =366) and healthy control individuals(NC group, n = 395). The polymorphism of rs2910164 genotyping results were analyzed,and OR(95% % CI) was calculated by unconditional logistic regression analysis. Results The frequencies of G allele were 56. 83% and 55. 18% in NC and T2DM group(P>0. 05). The frequencies of GG,GC and CC genotype were 31. 39%, 50.88%, and 17. 72% in NC group, and 30.31%, 49. 74%, and 19. 95% in T2DM group(P>0.05). The G allele and GG genotype were higher in DPN group than in NC and T2DM group(P<0.05). Logistic regression analysis showed that DPN risk was higher in GG genotype after adjusting age,duration,HbA1c [OR(95%CI)2. 34(1. 12～4. 82),P=0.013]. Individuals with the GG genotype had significantly higher SBP, FPG, HbA1c, UACR, HOMA-IR, longer diabetes duration and lower expression levels of miR-146 a. Binary logistic regression analysis showed that the miR-146 a rs2910164, HbA1c and diabetes duration were risk factors for DPN. Conclusion GG genotype in miR-146 a rs2910164 may decrease miR-146 a expression level and have a certain relationship with duration, HbA1c and HOMA-IR, thus increase the genetic susceptibility to DPN.

引文

[1] Galloway C, Chattopadhyay M. Increases in inflammatory mediators in DRG implicate in the pathogenesis of painful neuropathy in type 2 diabetes. Cytokine,2013,63:1-5.
    [2]吴群励,梁晓春.血红素加氧酶-1与糖尿病周围神经病变的研究进展.中国糖尿病杂志,2015,23:653-656.
    [3] Mu ZP, Wang YG, Li CQ, et al. Association between tumor necrosis factor-αand diabetic peripheral neuropathy in patients with type 2 diabetes:A meta-analysis. Mol Neurobiol,2017,54:983-996.
    [4] Veera GY, Geeta N, Shyam S, et al. Potential therapeutic effects of the simultaneous targeting of the Nrf2 and NF-κB pathways in diabetic neuropathy. Redox Biol, 2013,1:394-397.
    [5] Sandireddy R, Yerra VG, Areti A, et al. Neuroinflammation and oxidative stress in diabetic neuropathy:Futuristic strategies based on these targets. Int J Endocrinol, 2014,2014:674987.
    [6]王国凤,徐宁,杨涛.miR-146a在2型糖尿病周围神经病变患者外周血单个核细胞中的异常表达及临床意义.中华内分泌代谢杂志,2015, 31:748-751.
    [7]王国凤,徐宁,杨涛.外周血单个核细胞miR-146a变化与糖尿病周围神经病变的相关性研究.中国糖尿病杂志,2016, 24:532-535.
    [8]王国凤,徐宁,杨涛.外周血单个核细胞miR-146a在2型糖尿病周围神经病变发病机制中的作用.中华内分泌代谢杂志,2016, 32:552-555.
    [9] Jazdzewski W, Murray EL, Franssils K, et al. Common SNP inpre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA, 2008,105:7269-7274.
    [10] Han M, Zheng Y. Comprehensive analysis of single nucleotide polymorphisms and microRNAs:New direction in molecular epidemiology of solid cancer. J Cell Mol Med 2012, 16:8-21.
    [11] Wang L,Chopp M, Szalad A,et al. The role of miR-146a in dorsal root ganglia neurons of experimental diabetic peripheral neuropathy. Neuroscience, 2014,259:155-163.
    [12] Yousefzadeh N, Alipour MR, Soufi FG. Deregulation of NF-kB-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy. J Physiol Biochem. 2015, 71:51-58.
    [13] Alipoor B, Meshkani R, Ghaedi H, et al. Association of miR-146a rs2910164 and miR-149 rs2292832 variants with susceptibility to type 2 Diabetes. Clin Lab,2016,62:1553-1561.
    [14] Ciccacci C, Morganti R, Fusco DD,et al. Common polymor phisms in MIR146a, MIR128a and MIR27a genes contribute to neuropathy susceptibility in type 2 diabetes. Acta Diabetol. 2014, 51:663-671.
    [15]李奕平,杨曼,熊煜欣,等.miR-124a和miR-146基因多态性与中国人群代谢综合征的相关性研究.中国糖尿病杂志,2017,25:289-290.