Our aim was to evaluate in a cohort of 125 Italian patients with type 2 diabetes (T2D), who underwent neurological evaluation, the possible differences in the number of mitochondrial DNA copies (mtDNA) comparing positive and negative patients for cardiovascular autonomic neuropathy (CAN) or diabetic peripheral neuropathy (DPN) and comparing them with healthy controls. We also investigated a possible correlation of the number of mtDNA copies with the polymorphism rs3746444 of the MIR499A. T2D patients show a decrease in the number of mtDNA copies compared to healthy controls (p = 2 × 10⁻¹⁰). Dividing the T2D subjects by neurological evaluation, we found a significant mtDNA decrease in patients with DPN compared with those without (p = 0.02), while no differences were observed between subjects with and without CAN. Furthermore, the homozygous variant genotype for the polymorphism rs3746444 of MIR499A correlates with a decrease in the number of mtDNA copies, particularly in T2D patients (p = 0.009). Our data show a decrease in the number of mtDNA copies in subjects with T2D and suggest that this decrease is more evident in patients who develop DPN. Furthermore, the association of the variant allele of MIR499A with the number of mtDNA copies allows us to hypothesize a possible effect of this polymorphism in oxidative stress.

中文翻译：

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2型糖尿病多发性神经病患者的外周血线粒体DNA拷贝数减少，并且与MIR499A基因多态性相关。

我们的目的是评估一组125位接受过神经系统评估的意大利2型糖尿病（T2D）患者，比较阳性和阴性患者的心血管自主神经病（CAN）的线粒体DNA拷贝数（mtDNA）可能存在差异或糖尿病周围神经病变（DPN），并将其与健康对照进行比较。我们还调查了线粒体DNA复制与多态性rs3746444数量的可能的相关MIR499A。与健康对照相比，T2D患者显示mtDNA拷贝数减少（p  = 2×10 ^-10）。通过神经系统评估对T2D受试者进行划分，我们发现DPN患者的mtDNA与非DPN患者相比明显降低（p = 0.02），而在有和没有CAN的受试者之间未观察到差异。此外，对于多态性rs3746444的纯合子的基因型变体MIR499A与mtDNA的拷贝数的减少，特别是在T2D患者（相关p  = 0.009）。我们的数据显示患有T2D的受试者的mtDNA拷贝数减少，这表明这种减少在患有DPN的患者中更为明显。此外，MIR499A的变异等位基因与mtDNA拷贝数的关联使我们能够假设这种多态性在氧化应激中的可能作用。