title: Association of AluYb8 insertion/deletion polymorphism in the MUTYH gene with mtDNA maintain in the type 2 diabetes mellitus patients.
abstract: 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.
authors.affiliation: 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.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Bixia
authors.initials: B
authors.lastname: Zheng
authors.affiliation: 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.
authors.forename: Dong
authors.initials: D
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Cai
authors.affiliation: 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. Electronic address: wangyap@nju.edu.cn.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D020087:Alu Elements; D045647:DNA Glycosylases / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase
keywords: AluYb8 element; Base excision repair; MUTYH; Type 2 diabetes mellitus; mtDNA content; mtDNA maintain