Guo Wenwen, Zheng Bixia, Guo Dong, Cai Zhenming, Wang Yaping
Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, No.22 HanKou Road, Nanjing 210093, China; Department of Medical Genetics, Nanjing University School of Medicine, No.22 HanKou Road, Nanjing 210093, China; Clinical Molecular Diagnostic Center, Second Hospital, Nanjing Medical University, No.121 Jiangjiayuan Road, Nanjing 210011, China.
Jiangsu Key Laboratory of Molecular Medicine, Nanjing University School of Medicine, No.22 HanKou Road, Nanjing 210093, China; Department of Medical Genetics, Nanjing University School of Medicine, No.22 HanKou Road, Nanjing 210093, China.
Mol Cell Endocrinol. 2015 Jul 5;409:33-40. doi: 10.1016/j.mce.2015.03.019. Epub 2015 Mar 27.
A common AluYb8-element insertion/deletion polymorphism of the MUTYH gene (AluYb8MUTYH) is a novel genetic risk factor for type 2 diabetes mellitus (T2DM). In the present study, mtDNA sequencing analysis indicated that the mtDNA sequence heteroplasmy was not associated with AluYb8MUTYH polymorphism. To better understand the genetic risk for T2DM, we investigated the association of this polymorphism with mtDNA content, mtDNA breakage and mtDNA transcription in the leukocytes of T2DM patients. The mtDNA content and unbroken mtDNA were significantly increased in the mutant patients than in the wild-type patients (P <0.05, respectively). However, no association between mtDNA transcription and AluYb8MUTYH variant was observed. The results suggested that the AluYb8MUTYH variant was associated with an altered mtDNA maintain in T2DM patients. The high level of mtDNA content observed in the mutant patients may have resulted from inefficient base excision repair of mitochondrial MUTYH and a compensatory mechanism that is triggered by elevated oxidative stress.
MUTYH基因常见的AluYb8元件插入/缺失多态性（AluYb8MUTYH）是2型糖尿病（T2DM）的一种新型遗传风险因素。在本研究中，线粒体DNA（mtDNA）测序分析表明，mtDNA序列异质性与AluYb8MUTYH多态性无关。为了更好地了解T2DM的遗传风险，我们研究了这种多态性与T2DM患者白细胞中mtDNA含量、mtDNA断裂及mtDNA转录的相关性。突变患者的mtDNA含量和完整mtDNA均显著高于野生型患者（P均<0.05）。然而，未观察到mtDNA转录与AluYb8MUTYH变异之间存在关联。结果表明，AluYb8MUTYH变异与T2DM患者mtDNA维持改变有关。突变患者中观察到的高水平mtDNA含量可能是由于线粒体MUTYH碱基切除修复效率低下以及氧化应激升高触发的一种补偿机制所致。
