scholarly journals Insulinemic Potential of Lifestyle Is Inversely Associated with Leukocyte Mitochondrial DNA Copy Number in US White Adults

2020 ◽  
Vol 150 (8) ◽  
pp. 2156-2163 ◽  
Author(s):  
Keming Yang ◽  
Michele R Forman ◽  
Patrick O Monahan ◽  
Brett H Graham ◽  
Andrew T Chan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Epidemiologic Study ◽  
Health Study ◽  
Blood Collection ◽  
Inverse Association ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
White Adults

ABSTRACT Background Poor lifestyles have been linked to insulin insensitivity/hyperinsulinemia, which may contribute to downstream changes such as inflammation and oxidative damage and the development of chronic diseases. As a biomarker of intracellular oxidative stress, leukocyte mitochondrial DNA copy number (mtDNA-CN) has been related to lifestyle factors including diet and weight. No epidemiologic study has examined the relation between combined insulinemic potential of lifestyle and mtDNA-CN. Objectives Our aim was to examine the association between Empirical Lifestyle Index for Hyperinsulinemia (ELIH) and leukocyte mtDNA-CN in US men and women. Methods This cross-sectional analysis included 2835 white adults without cancers, diabetes, or cardiovascular disease at blood collection, including 2160 women from the Nurses’ Health Study and 675 men from the Health Professionals Follow-Up Study. ELIH is an index based on plasma C-peptide that characterizes the insulinemic potential of lifestyle (diet, body weight, and physical activity). Relative mtDNA-CN in peripheral blood leukocytes was measured by qPCR-based assay. Results We found a significant inverse association between ELIH and mtDNA-CN. In multivariable-adjusted linear models, absolute least squares means ± SDs of mtDNA-CN z score across ELIH quintiles in women were as follows: Q1: 0.14 ± 0.05; Q2: 0.04 ± 0.06; Q3: 0.008 ± 0.05; Q4: 0.01 ± 0.05; and Q5: −0.06 ± 0.05 (P-trend = 0.006). Means ± SDs in men were as follows: Q1: 0.25 ± 0.09; Q2: 0.23 ± 0.09; Q3: 0.07 ± 0.09; Q4: 0.02 ± 0.09; and Q5: −0.04 ± 0.09 (P-trend = 0.007). Means ± SDs in all participants were as follows: Q1: 0.16 ± 0.05; Q2: 0.07 ± 0.05; Q3: 0.01 ± 0.05; Q4: 0.01 ± 0.05; and Q5: −0.05 ± 0.05 (P-trend = 0.0004). Conclusions Hyperinsulinemic lifestyles (i.e., higher ELIH) were associated with lower leukocyte mtDNA-CN among subjects without major diseases, suggesting that the difference in lifestyle insulinemic potential may be related to excessive oxidative stress damage.

Mitochondrial DNA copy number correlates with oxidative stress and predicts mortality in nondiabetic hemodialysis patients

2010 ◽  
Vol 24 (3) ◽  
pp. 351-358 ◽  
Author(s):  
Yi-Chun Wang ◽  
Wen-Chin Lee ◽  
Shang-Chih Liao ◽  
Lung-Chih Lee ◽  
Yu-Jen Su ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dna ◽  
Copy Number ◽  
Hemodialysis Patients ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number

Mitochondrial DNA Copy Number in Peripheral Blood in the First Trimester of Pregnancy and Different Preeclampsia Clinical Phenotypes Development: A Pilot Study

2018 ◽  
Vol 26 (8) ◽  
pp. 1054-1061 ◽  
Author(s):  
Andrea Busnelli ◽  
Debora Lattuada ◽  
Stefania Ferrari ◽  
Marco Reschini ◽  
Barbara Colciaghi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dna ◽  
Peripheral Blood ◽  
Copy Number ◽  
First Trimester ◽  
Control Group ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
First Trimester Of Pregnancy ◽  
And Oxidative Stress

Inflammation and oxidative stress are intrinsically linked to early poor placentation, typical of pregnancies complicated by preeclampsia associated with intrauterine growth restriction (PE-IUGR). Low mitochondrial DNA copy number (mtDNAcn) in peripheral blood constitutes a good peripheral surrogate marker of inflammation and oxidative stress. On these basis, we explored a possible correlation between mtDNAcn in peripheral blood in the first trimester of pregnancy and the PE-IUGR onset. To shed light on this issue, we setup a nested case–control study from a prospective cohort of pregnant women undergoing first-trimester aneuploidies screening. Two groups of patients affected by PE classified according to the clinical phenotype were identified: (1) patients who developed PE-IUGR and (2) patients who developed PE associated with appropriate for gestational age intrauterine fetal growth (PE-AGAf). Controls were women with a physiologic pregnancy matched to cases on the basis of age (±6 months, ratio 2:1). Mitochondrial DNA copy number was quantified using real-time polymerase chain reaction and normalized to nuclear DNA. The median (interquartile range) mtDNAcn in peripheral blood in patients with PE-IUGR (n = 12) and in patients with PE-AGAf (n = 16) was 70 (44-97) and 108 (95-145), respectively ( P = .004). Both these values were significantly lower than that detected in the control group (161[133-183], P < .001). The area under the receiver–operator curve for PE-IUGR and PE-AGAf were 0.94 (95% confidence interval [CI]: 0.88-1.00, P < .001) and 0.81 (95%CI: 0.70-0.91, P < .001), respectively. In conclusion, MtDNAcn in peripheral blood resulted significantly lower both in patients affected by PE-IUGR and in those affected by PE-AGAf when compared to controls. The accuracy of this biomarker resulted particularly good in predicting PE-IUGR.

scholarly journals Mitochondrial DNA Copy Number and Risk of Gastric Cancer: a Report from the Shanghai Women's Health Study

2011 ◽  
Vol 20 (9) ◽  
pp. 1944-1949 ◽  
Author(s):  
Linda M. Liao ◽  
Andrea Baccarelli ◽  
Xiao-Ou Shu ◽  
Yu-Tang Gao ◽  
Bu-Tian Ji ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Mitochondrial Dna ◽  
Women’S Health ◽  
Women's Health ◽  
Copy Number ◽  
Health Study ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number

scholarly journals Particulate Air Pollution, Blood Mitochondrial DNA Copy Number, and Telomere Length in Mothers in the First Trimester of Pregnancy: Effects on Fetal Growth

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
S. Iodice ◽  
M. Hoxha ◽  
L. Ferrari ◽  
I. F. Carbone ◽  
C. Anceschi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dna ◽  
Birth Weight ◽  
Telomere Length ◽  
Fetal Growth ◽  
Copy Number ◽  
First Trimester ◽  
Dna Copy Number ◽  
Mitochondrial Dna Copy Number ◽  
First Trimester Of Pregnancy

Growing evidences have shown that particulate matter (PM) exposures during pregnancy are associated with impaired fetal development and adverse birth outcomes, possibly as a result of an exaggerated systemic oxidative stress and inflammation. Telomere length (TL) is strongly linked to biological age and is impacted by oxidative stress. We hypothesized that PM exposure during different time windows in the first trimester of pregnancy influences both mitochondrial DNA copy number (mtDNAcn), an established biomarker for oxidative stress, and TL. Maternal blood TL and mtDNAcn were analysed in 199 healthy pregnant women recruited at the 11th week of pregnancy by quantitative polymerase chain reaction. We also examined whether maternal mtDNAcn and TL were associated with fetal growth outcomes measured at the end of the first trimester of pregnancy (fetal heart rate, FHR; crown-rump length, CRL; and nuchal translucency, NT) and at delivery (birth weight, length, head circumference). The possible modifying effect of prepregnancy maternal body mass index was evaluated. PM10 exposure during the first pregnancy trimester was associated with an increased maternal mtDNAcn and a reduced TL. As regards ultrasound fetal outcomes, both FHR and CRL were positively associated with PM2.5, whereas the association with FHR was confirmed only when examining PM10 exposure. PM10 was also associated with a reduced birth weight. While no association was found between mtDNAcn and CRL, we found a negative relationship between mtDNAcn and fetal CRL only in overweight women, whereas normal-weight women exhibited a positive, albeit nonsignificant, association. As abnormalities of growth in utero have been associated with postnatal childhood and adulthood onset diseases and as PM is a widespread pollutant relevant to the large majority of the human population and obesity a rising risk factor, our results, if confirmed in a larger population, might represent an important contribution towards the development of more targeted public health strategies.

scholarly journals Blood-derived mitochondrial DNA copy number is associated with gene expression across multiple tissues and is predictive for incident neurodegenerative disease

2020 ◽  
Author(s):  
Stephanie Y. Yang ◽  
Christina A. Castellani ◽  
Ryan J. Longchamps ◽  
Vamsee K. Pillalamarri ◽  
Brian O’Rourke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mitochondrial Dna ◽  
Neurodegenerative Disease ◽  
Whole Blood ◽  
Copy Number ◽  
Rna Binding ◽  
Inverse Association ◽  
Dna Copy Number ◽  
Related Disease ◽  
Mitochondrial Dna Copy Number

ABSTRACTBackgroundMitochondrial DNA copy number (mtDNA-CN) can be used as a proxy for mitochondrial function and is associated with a number of aging-related diseases. However, it is unclear how mtDNA-CN measured in blood can reflect risk for diseases that primarily manifest in other tissues. Using the Genotype-Tissue Expression Project, we interrogated the relationships between mtDNA-CN measured in whole blood and gene expression from whole blood as well as 47 additional tissues.ResultsWe evaluated associations between blood-derived mtDNA-CN and gene expression in whole blood for 418 individuals, correcting for known confounders and surrogate variables derived from RNA-sequencing. Using a permutation-derived cutoff (p<2.70e-6), mtDNA-CN was significantly associated with expression for 721 genes in whole blood, including nuclear genes that are required for mitochondrial DNA replication. Significantly enriched pathways included splicing (p=1.03e-8) and ubiquitin-mediated proteolysis (p=2.4e-10). Genes with target sequences for the mitochondrial transcription factor NRF1 were also enriched (p=1.76e-35).In non-blood tissues, there were more significantly associated genes than expected in 30 out of 47 tested tissues, suggesting that global gene expression in those tissues is correlated with mtDNA-CN. Pathways that were associated in multiple tissues included RNA-binding, catalysis, and neurodegenerative disease. We evaluated the association between mtDNA-CN and incident neurodegenerative disease in an independent dataset, the UK Biobank, using a Cox proportional-hazards model. Higher mtDNA-CN was significantly associated with lower risk for incident neurodegenerative disease (HR=0.73, 95% CI= 0.66;0.90).ConclusionsThe observation that mtDNA-CN measured in whole blood is associated with gene expression in other tissues suggests that blood-derived mtDNA-CN can reflect metabolic health across multiple tissues. Key pathways in maintaining cellular homeostasis, including splicing, RNA binding, and catalytic genes were significantly associated with mtDNA-CN, reinforcing the importance of mitochondria in aging-related disease. As a specific example, genes involved in neurodegenerative disease were significantly enriched in multiple tissues. This finding, validated in a large independent cohort study showing an inverse association between mtDNA-CN and neurodegenerative disease, solidifies the link between blood-derived mtDNA-CN, altered gene expression in both blood and non-blood tissues, and aging-related disease.

scholarly journals Oxidative Stress Biomarkers and Mitochondrial DNA Copy Number Associated with APOE4 Allele and Cholinesterase Inhibitor Therapy in Patients with Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1971
Author(s):  
Chia-Wei Liou ◽  
Shih-Hsuan Chen ◽  
Tsu-Kung Lin ◽  
Meng-Han Tsai ◽  
Chiung-Chih Chang
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dna ◽  
Cholinesterase Inhibitor ◽  
Copy Number ◽  
Inhibitor Therapy ◽  
Dna Copy Number ◽  
Oxidative Stress Biomarkers ◽  
Apoe4 Allele ◽  
Stress Biomarkers ◽  
Mitochondrial Dna Copy Number

Studies of the oxidative/anti-oxidative status in patients with Alzheimer’s disease (AD) carrying different alleles of the apolipoprotein E (APOE) gene are currently inconclusive; meanwhile, data regarding mitochondrial DNA copy number (mtCN) remain limited. We herein determined the thiobarbituric acid reactive substances (TBARS), thiols, and mtCN in blood samples of 600 AD patients and 601 controls. A significantly higher oxidative TBARS (1.64 μmol/L), lower antioxidative thiols (1.60 μmol/L), and lower mtCN (2.34 log Delta Ct) were found in the AD cohort as compared to the non-AD cohort (1.54 μmol/L, 1.71 μmol/L, 2.46 log Delta Ct). We further identified the ε4 alleles (APOE4) and separated subjects into three groups according to the number of APOE4. A significant trend was noted in the TBARS levels of both AD and non-AD cohorts, highest in the homozygous two alleles (1.86 and 1.80 μmol/L), followed by heterozygous one allele (1.70 and 1.74 μmol/L), and lowest in the no APOE4 allele (1.56 and 1.48 μmol/L). Similar trends of lower thiols and mtCN were also found in the AD cohort. In our study of the influence of cholinesterase inhibitor therapy, we found significantly reduced TBARS levels, and elevated mtCN in AD patients receiving rivastigmine and galantamine therapy. Our study demonstrates associations between the APOE4 allele and oxidative stress biomarkers and mtCN. Using cholinesterase inhibitor therapy may benefit AD patients through attenuation of oxidative stress and manipulation of the mtCN.

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