DNA methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adults

Obesity is a major risk factor for cardiovascular disease. Blood-detected epigenetic profiles may serve as non-invasive clinically relevant biomarkers. Therefore, we investigated DNA methylation of genes involved in inflammation in peripheral blood of obese subjects and lean controls and their corre...

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Main Authors: Mohamed M. Ali, Dina Naquiallah, Maryam Qureshi, Mohammed Imaduddin Mirza, Chandra Hassan, Mario Masrur, Francesco M. Bianco, Patrice Frederick, Giulianotti P. Cristoforo, Antonio Gangemi, Shane A. Phillips, Abeer M. Mahmoud
Format: Article
Language:English
Published: Taylor & Francis Group 2022-01-01
Series:Epigenetics
Subjects:
Online Access:http://dx.doi.org/10.1080/15592294.2021.1876285
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author Mohamed M. Ali
Dina Naquiallah
Maryam Qureshi
Mohammed Imaduddin Mirza
Chandra Hassan
Mario Masrur
Francesco M. Bianco
Patrice Frederick
Giulianotti P. Cristoforo
Antonio Gangemi
Shane A. Phillips
Abeer M. Mahmoud
author_facet Mohamed M. Ali
Dina Naquiallah
Maryam Qureshi
Mohammed Imaduddin Mirza
Chandra Hassan
Mario Masrur
Francesco M. Bianco
Patrice Frederick
Giulianotti P. Cristoforo
Antonio Gangemi
Shane A. Phillips
Abeer M. Mahmoud
author_sort Mohamed M. Ali
collection DOAJ
description Obesity is a major risk factor for cardiovascular disease. Blood-detected epigenetic profiles may serve as non-invasive clinically relevant biomarkers. Therefore, we investigated DNA methylation of genes involved in inflammation in peripheral blood of obese subjects and lean controls and their correlation with cardiometabolic measurements. We obtained blood and adipose tissue (AT) samples from bariatric patients (n = 24) and control adults (n = 24). AT-isolated arterioles were tested for flow-induced dilation (FID) and production of nitric oxide (NO) and reactive oxygen species (ROS). Brachial artery flow-mediated dilation (FMD) was measured via doppler ultrasound. Promoter methylation of 94 genes involved in inflammation and autoimmunity were analysed in whole-blood DNA in relation to vascular function and cardiometabolic risk factors. 77 genes had ahigher methylated fraction in the controls compare obese subjects and 28 proinflammatory genes were significantly hypomethylated in the obese individuals; on top of these genes are CXCL1, CXCL12, CXCL6, IGF2BP2, HDAC4, IL12A, and IL17RA. Fifteen of these genes had significantly higher mRNA in obese subjects compared to controls; on top of these genes are CXCL6, TLR5, IL6ST, EGR1, IL15RA, and HDAC4. Methylation % inversely correlated with BMI, total fat %, visceral fat%, blood pressure, fasting plasma insulin, serum IL6 and C-reactive protein, arteriolar ROS, and alcohol consumption and positive correlations with lean %, HDL, plasma folate and vitamin B12, arteriolar FID and NO production, and brachial FMD. Our results suggest that vascular dysfunction in obese adults may be attributed to asystemic hypomethylation and over expression of the immune-related genes.
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spelling doaj.art-8502b0c6ff05487a8952fd5a0e7146852023-09-21T13:09:25ZengTaylor & Francis GroupEpigenetics1559-22941559-23082022-01-011719310910.1080/15592294.2021.18762851876285DNA methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adultsMohamed M. Ali0Dina Naquiallah1Maryam Qureshi2Mohammed Imaduddin Mirza3Chandra Hassan4Mario Masrur5Francesco M. Bianco6Patrice Frederick7Giulianotti P. Cristoforo8Antonio Gangemi9Shane A. Phillips10Abeer M. Mahmoud11College of Applied Health Sciences, University of Illinois at ChicagoCollege of Medicine, University of Illinois at ChicagoCollege of Medicine, University of Illinois at ChicagoCollege of Medicine, University of Illinois at ChicagoUniversity of Illinois at ChicagoUniversity of Illinois at ChicagoUniversity of Illinois at ChicagoUniversity of Illinois at ChicagoUniversity of Illinois at ChicagoUniversity of Illinois at ChicagoCollege of Applied Health Sciences, University of Illinois at ChicagoCollege of Medicine, University of Illinois at ChicagoObesity is a major risk factor for cardiovascular disease. Blood-detected epigenetic profiles may serve as non-invasive clinically relevant biomarkers. Therefore, we investigated DNA methylation of genes involved in inflammation in peripheral blood of obese subjects and lean controls and their correlation with cardiometabolic measurements. We obtained blood and adipose tissue (AT) samples from bariatric patients (n = 24) and control adults (n = 24). AT-isolated arterioles were tested for flow-induced dilation (FID) and production of nitric oxide (NO) and reactive oxygen species (ROS). Brachial artery flow-mediated dilation (FMD) was measured via doppler ultrasound. Promoter methylation of 94 genes involved in inflammation and autoimmunity were analysed in whole-blood DNA in relation to vascular function and cardiometabolic risk factors. 77 genes had ahigher methylated fraction in the controls compare obese subjects and 28 proinflammatory genes were significantly hypomethylated in the obese individuals; on top of these genes are CXCL1, CXCL12, CXCL6, IGF2BP2, HDAC4, IL12A, and IL17RA. Fifteen of these genes had significantly higher mRNA in obese subjects compared to controls; on top of these genes are CXCL6, TLR5, IL6ST, EGR1, IL15RA, and HDAC4. Methylation % inversely correlated with BMI, total fat %, visceral fat%, blood pressure, fasting plasma insulin, serum IL6 and C-reactive protein, arteriolar ROS, and alcohol consumption and positive correlations with lean %, HDL, plasma folate and vitamin B12, arteriolar FID and NO production, and brachial FMD. Our results suggest that vascular dysfunction in obese adults may be attributed to asystemic hypomethylation and over expression of the immune-related genes.http://dx.doi.org/10.1080/15592294.2021.1876285dna methylationobesityinflammationvascular functionflow-induced dilationcardiometabolic risk
spellingShingle Mohamed M. Ali
Dina Naquiallah
Maryam Qureshi
Mohammed Imaduddin Mirza
Chandra Hassan
Mario Masrur
Francesco M. Bianco
Patrice Frederick
Giulianotti P. Cristoforo
Antonio Gangemi
Shane A. Phillips
Abeer M. Mahmoud
DNA methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adults
Epigenetics
dna methylation
obesity
inflammation
vascular function
flow-induced dilation
cardiometabolic risk
title DNA methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adults
title_full DNA methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adults
title_fullStr DNA methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adults
title_full_unstemmed DNA methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adults
title_short DNA methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adults
title_sort dna methylation profile of genes involved in inflammation and autoimmunity correlates with vascular function in morbidly obese adults
topic dna methylation
obesity
inflammation
vascular function
flow-induced dilation
cardiometabolic risk
url http://dx.doi.org/10.1080/15592294.2021.1876285
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