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Mitochondrial DNA 4977bp deletion mutation in peripheral blood reflects atrial remodeling in patients with non-valvular atrial fibrillation

 Jihei Sara Lee  ;  Young-Guk Ko  ;  Kyoung-Jin Shin  ;  Sook-Kyoung Kim  ;  Jae Hyung Park  ;  Ki-Cheol Hwang  ;  Hui-Nam Pak 
 YONSEI MEDICAL JOURNAL, Vol.56(1) : 53-61, 2015 
Journal Title
Issue Date
Adult ; Aged ; Atrial Fibrillation/blood ; Atrial Fibrillation/genetics* ; Atrial Fibrillation/physiopathology* ; Atrial Remodeling/genetics* ; Base Pairing/genetics* ; Case-Control Studies ; DNA, Mitochondrial/blood* ; DNA, Mitochondrial/genetics* ; Female ; Heart Atria/pathology ; Heart Atria/physiopathology ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Mutation Rate ; Phenotype ; Sequence Deletion/genetics*
4977bp deletion mutation ; Atrial fibrillation ; atrial remodeling ; mitochondrial DNA
PURPOSE: 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.
MATERIALS AND 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.
CONCLUSION: 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.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Forensic Medicine (법의학과) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Ko, Young Guk(고영국) ORCID logo https://orcid.org/0000-0001-7748-5788
Kim, Sook Kyoung(김숙경)
Park, Jae Hyung(박재형)
Pak, Hui Nam(박희남) ORCID logo https://orcid.org/0000-0002-3256-3620
Shin, Kyoung Jin(신경진) ORCID logo https://orcid.org/0000-0002-1059-9665
Hwang, Ki Chul(황기철)
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