Role of mitochondrial DNA variants and copy number in diabetic atherogenesis
Role of mitochondrial DNA variants and copy number in diabetic atherogenesis
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DOI：
10.4238/2012.september.17.4
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发表时间：
2012-01-01
影响因子：
0.4
通讯作者：
Weng, S. W.
中科院分区：
文献类型：
--
作者：
Chien, M. C.;Huang, W. T.;Weng, S. W.
高血糖诱导的活性氧产生可引起糖尿病及其并发症，包括动脉粥样硬化。线粒体DNA变异和线粒体拷贝数在糖尿病动脉粥样硬化发病机制中的作用尚不清楚。我们研究了36例因糖尿病足而截肢的糖尿病患者和7例因外伤而截肢的非糖尿病患者。提取线粒体DNA进行测序。分析了与剑桥参考序列的单核苷酸多态性。实时荧光定量PCR检测线粒体DNA拷贝数。29例糖尿病动脉狭窄患者中检出21个新变异；其中6个变异是异质的，大多数发生在高度进化保守的残基上。这些变异在动脉狭窄患者中比在没有动脉狭窄的患者中更为普遍。新变异包括复合物I中的四个（ND1: C3477A/C, A3523A/G; ND5: C13028A/C, C13060A/C），复合物IV中的一个（COX1: T6090A/T）和rRNA中的一个（12srRNA: G857G/T）。与非糖尿病患者相比，糖尿病患者线粒体DNA明显减少。此外，在动脉狭窄的糖尿病患者中，线粒体DNA拷贝数与总snp数呈显著正相关。总之，我们在动脉狭窄的糖尿病患者中发现了六种新的异质线粒体DNA变异，我们发现糖尿病动脉粥样硬化与线粒体DNA数量减少有关。
Hyperglycemia-induced reactive oxygen species production can cause diabetes and its complications, including atherosclerosis. The role of mitochondrial DNA variants and mitochondrial copy number in the pathogenesis of diabetic atherogenesis is not well understood. We examined 36 diabetic patients who had undergone amputation for diabetic foot and seven non-diabetic patients who had undergone amputation after traumatic injury. Mitochondrial DNA was extracted and used for sequencing. Single nucleotide polymorphisms (SNPs) relative to the Cambridge reference sequence were analyzed. Mitochondrial DNA copy number was quantified by real-time PCR. Twenty-one novel variants were detected in 29 diabetic patients with arterial stenosis; six of the variants were heteroplasmic, and most occurred in highly evolutionarily conserved residues. These variants were more prevalent in patients with arterial stenosis than in those without stenosis. The novel variants included four in complex I (ND1: C3477A/C, A3523A/G; ND5: C13028A/C, C13060A/C), one in complex IV (COX1: T6090A/T), and one in rRNA (12srRNA: G857G/T). Compared with non-diabetic patients, the diabetic patients had significantly less mitochondrial DNA. Furthermore, among diabetic patients with arterial stenosis, there was a significant positive correlation between mitochondrial DNA copy number and the number of total SNPs. In conclusion, we identified six novel heteroplasmic mitochondrial DNA variants among diabetic patients with arterial stenosis, and we found that diabetic atherogenesis is associated with decreased amounts of mitochondrial DNA.