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• W4362693106 abstract "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." @default.
• W4362693106 created "2023-04-09" @default.
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• W4362693106 date "2023-04-18" @default.
• W4362693106 modified "2023-09-23" @default.
• W4362693106 title "Characterization of the Mitochondrial Genetic Landscape in Abdominal Aortic Aneurysm" @default.
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• W4362693106 doi "https://doi.org/10.1161/jaha.122.029248" @default.
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• W4362693106 hasPublicationYear "2023" @default.
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