Circulating mitochondrial DNA

New indices of type 2 diabetes-related cognitive impairment in Mexican Americans

Research output: Contribution to journalArticleResearchpeer-review

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 (mtDNA CN ) 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 mtDNA CN 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. MtDNA CN 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 mtDNA CN . 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 mtDNA CN ) is intimately linked to both T2D and CI phenotypes as well as aging.

Original languageEnglish
Article numbere0213527
JournalPLoS ONE
Volume14
Issue number3
DOIs
StatePublished - 1 Mar 2019

Fingerprint

Mexican Americans
Medical problems
Mitochondrial DNA
noninsulin-dependent diabetes mellitus
Type 2 Diabetes Mellitus
mitochondrial DNA
Alzheimer disease
Single Nucleotide Polymorphism
Mitochondria
Disease Progression
Mucin-2
Alzheimer Disease
mitochondria
cells
Mitochondrial Dynamics
fatty acid-binding proteins
Fatty Acid-Binding Proteins
loci
Cognitive Dysfunction
Parkinson disease

Cite this

@article{ee997d5a7542497fb83b42cc93461bf4,
title = "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 (mtDNA CN ) 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 mtDNA CN 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. MtDNA CN 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 mtDNA CN . 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 mtDNA CN ) is intimately linked to both T2D and CI phenotypes as well as aging.",
author = "Talisa Silzer and Barber, {Robert Clinton} and Jie Sun and Gita Pathak and Johnson, {Leigh A.} and Sidney O'Bryant and Phillips, {Nicole Ruth}",
year = "2019",
month = "3",
day = "1",
doi = "10.1371/journal.pone.0213527",
language = "English",
volume = "14",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "3",

}

Circulating mitochondrial DNA : New indices of type 2 diabetes-related cognitive impairment in Mexican Americans. / Silzer, Talisa; Barber, Robert Clinton; Sun, Jie; Pathak, Gita; Johnson, Leigh A.; O'Bryant, Sidney; Phillips, Nicole Ruth.

In: PLoS ONE, Vol. 14, No. 3, e0213527, 01.03.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Circulating mitochondrial DNA

T2 - New indices of type 2 diabetes-related cognitive impairment in Mexican Americans

AU - Silzer, Talisa

AU - Barber, Robert Clinton

AU - Sun, Jie

AU - Pathak, Gita

AU - Johnson, Leigh A.

AU - O'Bryant, Sidney

AU - Phillips, Nicole Ruth

PY - 2019/3/1

Y1 - 2019/3/1

N2 - 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 (mtDNA CN ) 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 mtDNA CN 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. MtDNA CN 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 mtDNA CN . 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 mtDNA CN ) is intimately linked to both T2D and CI phenotypes as well as aging.

AB - 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 (mtDNA CN ) 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 mtDNA CN 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. MtDNA CN 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 mtDNA CN . 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 mtDNA CN ) is intimately linked to both T2D and CI phenotypes as well as aging.

UR - http://www.scopus.com/inward/record.url?scp=85062845230&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0213527

DO - 10.1371/journal.pone.0213527

M3 - Article

VL - 14

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 3

M1 - e0213527

ER -