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Characterization of the Mitochondrial Genetic Landscape in Abdominal Aortic Aneurysm.
Vats, Sakshi; Sundquist, Kristina; Li, Yanni; Wang, Xiao; Hong, Mun-Gwan; Sundquist, Jan; Zarrouk, Moncef; Gottsäter, Anders; Memon, Ashfaque A.
Affiliation
  • Vats S; Center for Primary Health Care Research, Department of Clinical Sciences Lund University/Region Skåne Malmö Sweden.
  • Sundquist K; Center for Primary Health Care Research, Department of Clinical Sciences Lund University/Region Skåne Malmö Sweden.
  • Li Y; Department of Family Medicine and Community Health, Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai New York NY.
  • Wang X; Center for Community-Based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine Shimane University Matsue Japan.
  • Hong MG; Center for Primary Health Care Research, Department of Clinical Sciences Lund University/Region Skåne Malmö Sweden.
  • Sundquist J; Center for Primary Health Care Research, Department of Clinical Sciences Lund University/Region Skåne Malmö Sweden.
  • Zarrouk M; National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Department of Biochemistry and Biophysics Stockholm University Solna Sweden.
  • Gottsäter A; Center for Primary Health Care Research, Department of Clinical Sciences Lund University/Region Skåne Malmö Sweden.
  • Memon AA; Department of Family Medicine and Community Health, Department of Population Health Science and Policy Icahn School of Medicine at Mount Sinai New York NY.
J Am Heart Assoc ; 12(8): e029248, 2023 04 18.
Article in En | MEDLINE | ID: mdl-37026541
Background Abdominal aortic aneurysm (AAA) is a vascular disease with a mortality rate of >80% if ruptured. Mitochondrial dysfunction has been previously implicated in AAA pathogenesis. In this study, we aimed to characterize the mitochondrial genetic landscape in AAA. Methods and Results Whole mitochondrial genome sequencing and bioinformatics analysis were performed in comorbidity matched 48 cases without AAA and 48 cases with AAA, objectively diagnosed, and selected from a cohort of 65-year-old men recruited for a screening program. We identified differential mutational landscapes in men with and without AAA, with errors in mitochondrial DNA replication or repair as potential sources. Heteroplasmic insertions and overall heteroplasmy of structural rearrangements were significantly elevated in AAA cases. Three heteroplasmic variants were associated with risk factors of AAA: leukocyte concentration, plasma glucose, and cholesterol levels, respectively. Interestingly, mutations were more prevalent in regulatory part of the mitochondria, the displacement loop region, in AAA as compared with controls (P value <0.05), especially in the conserved and critical mitochondrial extended termination-associated sequence region. Moreover, we report a novel 24 bp mitochondrial DNA duplication present exclusively in cases with AAA (4%) and 75% of the unmatched AAA biopsies. Finally, the haplogroup cluster JTU was overrepresented in AAA and significantly associated with a positive family history of AAA (odds ratio, 2.9 [95% CI, 1.1-8.1]). Conclusions This is the first study investigating the mitochondrial genome in AAA, where important genetic alterations and haplogroups associated with AAA and clinical risk factors were identified. Our findings have the potential to fill in gaps in the missing genetic information on AAA.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aortic Aneurysm, Abdominal Type of study: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Humans / Male Language: En Journal: J Am Heart Assoc Year: 2023 Document type: Article Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Aortic Aneurysm, Abdominal Type of study: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Limits: Aged / Humans / Male Language: En Journal: J Am Heart Assoc Year: 2023 Document type: Article Country of publication: