Background: BMI is a strong indicator of complications from type I diabetes, especially under intensive treatment.
Methods: We have genotyped 435 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays and performed mitoGWAS on BMI. We identified additive interactions between mitochondrial and nuclear variants in genes associated with mitochondrial functioning MitoCarta2.0 and confirmed and refined the results on external cohorts: the Framingham Heart Study (FHS) and GTEx data. Linear mixed model analysis was performed using the GENESIS package in R/Bioconductor.
Results: We find a borderline significant association between the mitochondrial variant rs28357980, localized to MT-ND2, and BMI (β = - 0.69, p = 0.056). This BMI association was confirmed on 1889 patients from FHS cohort (β = - 0.312, p = 0.047). Next, we searched for additive interactions between mitochondrial and nuclear variants. MT-ND2 variants interacted with variants in the genes SIRT3, ATP5B, CYCS, TFB2M and POLRMT. TFB2M is a mitochondrial transcription factor and together with TFAM creates a transcription promoter complex for the mitochondrial polymerase POLRMT. We have found an interaction between rs3021088 in MT-ND2 and rs6701836 in TFB2M leading to BMI decrease (inter_pval = 0.0241), while interaction of rs3021088 in MT-ND2 and rs41542013 in POLRMT led to BMI increase (inter_pval = 0.0004). The influence of these interactions on BMI was confirmed in external cohorts.
Conclusions: Here, we have shown that variants in the mitochondrial genome as well as additive interactions between mitochondrial and nuclear SNPs influence BMI in T1DM and general cohorts.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341625 | PMC |
| http://dx.doi.org/10.1186/s12920-020-00752-7 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione protects against MPP-induced neurotoxicity by ameliorating oxidative stress, apoptosis and autophagy in SH-SY5Y cells.
Metab Brain Dis
January 2025
Key Laboratory of Longevity and Aging-Related Disease of Chinese Ministry of Education, Center for Translational Medicine, School of Basic Medical Sciences, Guangxi Medical University, Nanning, Guangxi, China.
2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD) is a cyclohexanedione compound extracted from the roots of Averrhoa carambola L. Several studies have documented its beneficial effects on diabetes, Alzheimer's disease, and cancer. However, its potential neuroprotective effects on Parkinson's disease (PD) have not yet been explored.
View Article and Find Full Text PDFEffects of Tasimelteon Treatment on Traumatic Brain Injury Through NRF-2/HO-1 and RIPK1/RIPK3/MLKL Pathways in Rats.
Mol Neurobiol
January 2025
Department of Pathology, Faculty of Veterinary Medicine, Burdur Mehmet Akif Ersoy University, Burdur, Turkey.
Secondary brain damageafter traumatic brain injury (TBI) involves oxidative stress, neuroinflammation, apoptosis, and necroptosis and can be reversed by understanding these molecular pathways. The objective of this study was to examine the impact of tasimelteon (Tasi) administration on brain injury through the nuclear factor erythroid 2-related factor 2 (NRF-2)/heme oxygenase-1 (HO-1) and receptor-interacting protein kinase 1 (RIPK1)/receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like (MLKL) pathways in rats with TBI. Thirty-two male Wistar albino rats weighing 300-350 g were randomly divided into four groups: the control group, trauma group, Tasi-1 group (trauma + 1 mg/kg Tasi intraperitoneally), and Tasi-10 group (trauma + 10 mg/kg Tasi intraperitoneally).
View Article and Find Full Text PDFPhAsO as a Strong Hydrogen-Bond Acceptor in Cocrystals with Hydrogen Peroxide and Dihydroperoxides.
Inorg Chem
January 2025
Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia.
Hydrogen-bonded cocrystals have attracted considerable attention as they allow fine-tuning of properties through the choice of hydrogen-bond donors and acceptors. In this study, triphenylarsine oxide (PhAsO) is introduced as a strong hydrogen-bond acceptor molecule. Due to its higher Lewis basicity compared to triphenylphosphine oxide (PhPO), it acts as a strong hydrogen-bond acceptor, which is demonstrated in six new cocrystals with HO and -di(hydroperoxy)cycloalkanes.
View Article and Find Full Text PDFFragments of Community: Physician Assistant Student Perspectives on Experience of Community With Faculty.
J Physician Assist Educ
January 2025
Kaley Romero, PA-C, Metrolina Nephrology Associates, Charlotte, North Carolina.
Introduction: Burnout is prevalent among both physician assistant (PA) students and faculty in the United States. Theories concerning the root cause of this burnout include a breakdown of community, which, in this context, serves as a framework comprising membership, influence, integration and fulfilment of needs, and shared emotional connection. A community framework has yet to be formally applied to the PA learning environment.
View Article and Find Full Text PDFNeuro-computational simulation of blood flow loaded with gold and maghemite nanoparticles inside an electromagnetic microchannel under rapid and unexpected change in pressure gradient.
Electromagn Biol Med
January 2025
Department of Mathematics, University of Gour Banga, Malda, India.
In cardiovascular research, electromagnetic fields generated by Riga plates are utilized to study or manipulate blood flow dynamics, which is particularly crucial in developing treatments for conditions such as arterial plaque deposition and understanding blood behavior under varied flow conditions. This research predicts the flow patterns of blood enhanced with gold and maghemite nanoparticles (gold-maghemite/blood) in an electromagnetic microchannel influenced by Riga plates with a temperature gradient that decays exponentially, under sudden changes in pressure gradient. The flow modeling includes key physical influences like radiation heat emission and Darcy drag forces in porous media, with the flow mathematically represented through unsteady partial differential equations solved using the Laplace transform (LT) method.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!