title: Mitochondrial DNA 4977bp deletion mutation in peripheral blood reflects atrial remodeling in patients with non-valvular atrial fibrillation.
abstract: OBJECTIVE
  Recently, mitochondrial DNA 4977bp deletion (mtDNA4977-mut), a somatic mutation related to oxidative stress, has been shown to be associated with atrial fibrillation (AF). We hypothesized that patient age, as well as electroanatomical characteristics of fibrillating left atrial (LA), vary depending on the presence of mtDNA4977-mut in peripheral blood among patients with non-valvular AF.
  
  
  METHODS
  Analyzing clinical and electroanatomical characteristics, we investigated the presence of the mtDNA4977-mut in peripheral blood of 212 patients (51.1±13.2 years old, 83.5% male) undergoing catheter ablation for non-valvular AF, as well as 212 age-matched control subjects.
  
  
  RESULTS
  The overall frequency of peripheral blood mtDNA4977-mut in patients with AF and controls was not significantly different (24.5% vs. 19.3%, p=0.197). When the AF patient group was stratified according to age, mtDNA4977-mut was more common (47.4% vs. 20.0%, p=0.019) in AF patients older than 65 years than their age-matched controls. Among AF patients, those with mtDNA4977-mut were older (58.1±11.9 years old vs. 48.8±11.9 years old, p<0.001). AF patients positive for the mtDNA mutation had greater LA dimension (p=0.014), higher mitral inflow peak velocity (E)/diastolic mitral annular velocity (Em) ratio (p<0.001), as well as lower endocardial voltage (p=0.035), and slower conduction velocity (p=0.048) in the posterior LA than those without the mutation. In multivariate analysis, E/Em ratio was found to be significantly associated with the presence of mtDNA4977-mut in peripheral blood.
  
  
  CONCLUSIONS
  mtDNA4977-mut, an age-related somatic mutation detected in the peripheral blood, is associated with advanced age and electro-anatomical remodeling of the atrium in non-valvular AF.
authors.affiliation: Department of Internal Medicine, Yonsei Univerisity College of Medicine, Seoul, Korea.
authors.forename: Jihei Sara
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Yonsei Univerisity College of Medicine, Seoul, Korea. ygko@yuhs.ac.
authors.forename: Young-Guk
authors.initials: YG
authors.lastname: Ko
authors.affiliation: Department of Forensic Medicine, Yonsei Univerisity College of Medicine, Seoul, Korea. kjshin@yuhs.ac.
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Yonsei Univerisity College of Medicine, Seoul, Korea.
authors.forename: Sook-Kyoung
authors.initials: SK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei Univerisity College of Medicine, Seoul, Korea.
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Yonsei Univerisity College of Medicine, Seoul, Korea.
authors.forename: Ki-Cheol
authors.initials: KC
authors.lastname: Hwang
authors.affiliation: Department of Internal Medicine, Yonsei Univerisity College of Medicine, Seoul, Korea.
authors.forename: Hui-Nam
authors.initials: HN
authors.lastname: Pak
mesh_terms: D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood / Q000235:genetics* / Q000503:physiopathology*; D064752:Atrial Remodeling / Q000235:genetics*; D020029:Base Pairing / Q000235:genetics*; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000097:blood* / Q000235:genetics*; D005260:Female; D006325:Heart Atria / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D059645:Mutation Rate; D010641:Phenotype; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D004272:DNA, Mitochondrial
keywords: 4977bp deletion mutation; Atrial fibrillation; atrial remodeling; mitochondrial DNA