Elevations in Circulating Methylated and Unmethylated Preproinsulin DNA in New-Onset Type 1 Diabetes.
Elevations in Circulating Methylated and Unmethylated Preproinsulin DNA in New-Onset Type 1 Diabetes.
复制标题
DOI：
10.2337/db15-0430
复制
发表时间：
2015-11
期刊：
影响因子：
7.7
通讯作者：
Mirmira RG
中科院分区：
文献类型：
--
作者：
Fisher MM;Watkins RA;Blum J;Evans-Molina C;Chalasani N;DiMeglio LA;Mather KJ;Tersey SA;Mirmira RG
循环中未甲基化与甲基化前胰岛素原（INS）DNA的比率升高已被认为反映了1型糖尿病（T1D）中的β细胞死亡。我们检验了未甲基化和甲基化INS DNA的绝对水平（而不是比率）在新发T1D受试者和对照受试者之间存在差异的假设，并评估了这些参数的纵向变化。我们使用液滴数字PCR来测量T1D发作时以及发作后8周和1年受试者血清中未甲基化和甲基化INS DNA的水平。与对照组相比，T1D发作时未甲基化和甲基化INS DNA水平均升高。在发病后8周，甲基化INS DNA仍然升高，但未甲基化INS DNA下降。发病后1年，未甲基化和甲基化INS DNA均恢复至对照水平。肥胖、2型糖尿病和自身免疫性肝炎受试者的非甲基化和甲基化INS水平低于T1D受试者，与对照受试者相比无差异。我们的研究表明，未甲基化和甲基化INS DNA的升高发生在新发T1D中，并且这些DNA种类的水平在T1D进化过程中发生变化。我们的工作强调需要考虑差异甲基化DNA种类的绝对水平作为疾病的潜在生物标志物。
Elevated ratios of circulating unmethylated to methylated preproinsulin (INS) DNA have been suggested to reflect β-cell death in type 1 diabetes (T1D). We tested the hypothesis that absolute levels (rather than ratios) of unmethylated and methylated INS DNA differ between subjects with new-onset T1D and control subjects and assessed longitudinal changes in these parameters. We used droplet digital PCR to measure levels of unmethylated and methylated INS DNA in serum from subjects at T1D onset and at 8 weeks and 1 year post-onset. Compared with control subjects, levels of both unmethylated and methylated INS DNA were elevated at T1D onset. At 8 weeks post-onset, methylated INS DNA remained elevated, but unmethylated INS DNA fell. At 1 year postonset, both unmethylated and methylated INS DNA returned to control levels. Subjects with obesity, type 2 diabetes, and autoimmune hepatitis exhibited lower levels of unmethylated and methylated INS compared with subjects with T1D at onset and no differences compared with control subjects. Our study shows that elevations in both unmethylated and methylated INS DNA occurs in new-onset T1D and that levels of these DNA species change during T1D evolution. Our work emphasizes the need to consider absolute levels of differentially methylated DNA species as potential biomarkers of disease.