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Circulating mitochondrial DNA: New indices of type 2 diabetes-related cognitive impairment in Mexican Americans.

ABSTRACT: Mitochondrial function has been implicated and studied in numerous complex age-related diseases. Understanding the potential role of mitochondria in disease pathophysiology is of importance due to the rise in prevalence of complex age-related diseases, such as type 2 diabetes (T2D) and Alzheimer's disease (AD). These two diseases specifically share common pathophysiological characteristics which potentially point to a common root cause or factors for disease exacerbation. Studying the shared phenomena in Mexican Americans is of particular importance due to the disproportionate prevalence of both T2D and AD in this population. Here, we assessed the potential role of mitochondria in T2D and cognitive impairment (CI) in a Mexican American cohort by analyzing blood-based indices of mitochondrial DNA copy number (mtDNACN) and cell-free mitochondrial DNA (CFmtDNA). These mitochondrial metrics were also analyzed for correlation with relevant neuropsychological variables and physiological data collected as indicators of disease and/or disease progression. We found mtDNACN to be significantly decreased in individuals with CI, while CFmtDNA was significantly elevated in T2D; further, CFmtDNA elevation was significantly exacerbated in individuals with both diseases. MtDNACN was found to negatively correlate with age and fatty acid binding protein concentration, while positively correlating with CFmtDNA as well as CERAD total recall score. Candidate gene SNP-set analysis was performed on genes previously implicated in maintenance and control of mitochondrial dynamics to determine if nuclear variants may account for variability in mtDNACN. The results point to a single significant locus, in the LRRK2/MUC19 region, encoding leucine rich repeat kinase 2 and mucin 19. This locus has been previously implicated in Parkinson's disease, among others; rs7302859 was the driver SNP. These combined findings further indicate that mitochondrial dysfunction (as assessed by proxy via mtDNACN) is intimately linked to both T2D and CI phenotypes as well as aging.

SUBMITTER: Silzer T

PROVIDER: S-EPMC6414026 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Circulating mitochondrial DNA: New indices of type 2 diabetes-related cognitive impairment in Mexican Americans.

Silzer Talisa T Barber Robert R Sun Jie J Pathak Gita G Johnson Leigh L O'Bryant Sid S Phillips Nicole N

PloS one 20190312 3

Mitochondrial function has been implicated and studied in numerous complex age-related diseases. Understanding the potential role of mitochondria in disease pathophysiology is of importance due to the rise in prevalence of complex age-related diseases, such as type 2 diabetes (T2D) and Alzheimer's disease (AD). These two diseases specifically share common pathophysiological characteristics which potentially point to a common root cause or factors for disease exacerbation. Studying the shared phe ...[more]

PMID: 30861027

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Project description:Our objective was to compare neurological, functional, and cognitive stroke outcomes in Mexican Americans (MAs) and non-Hispanic whites using data from a population-based study.Ischemic strokes (2008-2012) were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) Project. Data were collected from patient or proxy interviews (conducted at baseline and 90 days poststroke) and medical records. Ethnic differences in neurological (National Institutes of Health Stroke Scale: range, 0-44; higher scores worse), functional (activities of daily living/instrumental activities of daily living score: range, 1-4; higher scores worse), and cognitive (Modified Mini-Mental State Examination: range, 0-100; lower scores worse) outcomes were assessed with Tobit or linear regression adjusted for demographics and clinical factors.A total of 513, 510, and 415 subjects had complete data for neurological, functional, and cognitive outcomes and covariates, respectively. Median age was 66 (interquartile range, 57-78); 64% were MAs. In MAs, median National Institutes of Health Stroke Scale, activities of daily living/instrumental activities of daily living, and Modified Mini-Mental State Examination score were 3 (interquartile range, 1-6), 2.5 (interquartile range, 1.6-3.5), and 88 (interquartile range, 76-94), respectively. MAs scored 48% worse (95% CI, 23%-78%) on National Institutes of Health Stroke Scale, 0.36 points worse (95% CI, 0.16-0.57) on activities of daily living/instrumental activities of daily living score, and 3.39 points worse (95% CI, 0.35-6.43) on Modified Mini-Mental State Examination than non-Hispanic whites after multivariable adjustment.MAs scored worse than non-Hispanic whites on all outcomes after adjustment for confounding factors; differences were only partially explained by ethnic differences in survival. These findings in combination with the increased stroke risk in MAs suggest that the public health burden of stroke in this growing population is substantial.

Dataset Information

Circulating mitochondrial DNA: New indices of type 2 diabetes-related cognitive impairment in Mexican Americans.

Publications

Circulating mitochondrial DNA: New indices of type 2 diabetes-related cognitive impairment in Mexican Americans.

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