编码miR-155和miR-146a的基因多态性与1型糖尿病的保护作用相关。
Polymorphisms in genes encoding miR-155 and miR-146a are associated with protection to type 1 diabetes mellitus.
作者信息
Assmann Taís S, Duarte Guilherme C K, Brondani Letícia A, de Freitas Pedro H O, Martins Égina M, Canani Luís H, Crispim Daisy
机构信息
Endocrine Division, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, prédio 12, 4° andar, Porto Alegre, Rio Grande do Sul, 90035-003, Brazil.
Postgraduation Program in Medical Sciences: Endocrinology, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.
出版信息
Acta Diabetol. 2017 May;54(5):433-441. doi: 10.1007/s00592-016-0961-y. Epub 2017 Jan 19.
AIMS
Type 1 diabetes mellitus (T1DM) is characterized by severe autoimmune destruction of pancreatic beta-cells. The triggering of autoimmunity against beta-cells is probably caused by a combination of environmental and genetic risk factors. Even though much is known about the genetic of T1DM, more information is needed to completely unravel this tangled disease. MicroRNAs (miRNAs) are a class of small noncoding RNAs molecules that negatively regulate gene expression by inducing target mRNA cleavage or by inhibiting protein translation. Abnormal miRNA expressions have been described in autoimmune diseases and T1DM. Polymorphisms in genes codifying miRNAs may alter the expression of the corresponding miRNA and, thus, confer susceptibility for a given disease. Therefore, the aim of this study was to investigate whether polymorphisms in genes encoding miR-155, miR-146a, and miR-375 are associated with T1DM.
METHODS
Frequencies of the miRNA-146a rs2910164, miRNA-155 rs767649 and miRNA-375 rs6715345 polymorphisms were analyzed in 490 T1DM patients and in 469 nondiabetic subjects.
RESULTS
The miR-146a rs2910164 and miR-155 rs767649 polymorphisms were associated with protection for T1DM, and the strongest association was observed for the dominant model [odds ratio (OR) = 0.557 95% CI 0.355-0.874 and OR = 0.508, 95% CI 0.265-0.973, respectively, after adjustment for age, ethnicity, and risk HLA loci]. However, miR-375 rs6715345 frequencies did not differ between cases and controls.
CONCLUSION
MiR-146a rs2910164 and miR-155 rs767649 polymorphisms were associated with protection for T1DM.
目的
1型糖尿病（T1DM）的特征是胰腺β细胞受到严重的自身免疫性破坏。针对β细胞的自身免疫反应的触发可能是由环境和遗传风险因素共同作用引起的。尽管对T1DM的遗传学已经有了很多了解，但仍需要更多信息来完全解开这种复杂的疾病。微小RNA（miRNA）是一类小的非编码RNA分子，通过诱导靶mRNA切割或抑制蛋白质翻译来负向调节基因表达。在自身免疫性疾病和T1DM中已经描述了miRNA表达异常。编码miRNA的基因中的多态性可能会改变相应miRNA的表达，从而赋予对特定疾病的易感性。因此，本研究的目的是调查编码miR-155、miR-146a和miR-375的基因中的多态性是否与T1DM相关。
方法
分析了490例T1DM患者和469例非糖尿病受试者中miRNA-146a rs2910164、miRNA-155 rs767649和miRNA-375 rs6715345多态性的频率。
结果
miR-146a rs2910164和miR-155 rs767649多态性与T1DM的保护作用相关，在调整年龄、种族和风险HLA位点后，显性模型的关联最强[比值比（OR）分别为0.557，95%可信区间0.355 - 0.874和OR = 0.508，95%可信区间0.265 - 0.973]。然而，miR-375 rs6715345的频率在病例组和对照组之间没有差异。
结论
MiR-146a rs2910164和miR-155 rs767649多态性与T1DM的保护作用相关。
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