THU0003 ALTERED DNA METHYLATION AND DIFFERENTIAL EXPRESSION OF GENES INFLUENCING CARDIOVASCULAR RISK AND IMMUNITY IN CD4+ T CELLS FROM SUBJECTS WITH PSORIATIC ARTHRITIS.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 214.1-214
Author(s):  
I. Arias de la Rosa ◽  
M. D. López Montilla ◽  
J. Rodríguez ◽  
E. Ballester ◽  
C. Torres-Granados ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Factors ◽  
Insulin Resistance ◽  
Dna Methylation ◽  
T Cells ◽  
Cardiovascular Risk ◽  
Research Support ◽  
Insulin Resistant ◽  
Genome Wide ◽  
Differentially Methylated Genes

Background:Cardiovascular risk factors are increased in Psoriatic Arthritis (PsA). In fact, around 60% out of PsA patients display insulin resistance (IR), a hallmark of metabolic syndrome, which might significantly contribute to the cardiovascular disease. Latest studies suggested that inflammatory and metabolic disorders may be under epigenetic control, including DNA methylation. DNA methylation is an unexplored area in the field of PsA.Objectives:To study the alterations in the genome-wide DNA methylation profile of CD4+T cells from PsA patients and its relationship with its pathology and the risk of cardiovascular comorbidity.Methods:Twenty healthy controls (HC) and 20 PsA patients were included in the study. PsA patients were classified into insulin resistant and non-insulin resistant according to HOMA-IR index. CD4+T lymphocytes were isolated from peripheral blood by positive immunomagnetic selection. The Illumina Infinium MethylationEPIC Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs (TSS1500, TSS200, 5UTR, 3UTR, first exon, gene body). Beta values (β) estimating methylation levels were obtained at each CpG site, and differentially methylated genes (DMG) between PsA and HC were identified. Functional classification of these genes was carried out through gene ontology analysis (PANTHER database). Gene expression analysis of the selected genes was also evaluated by RT-PCR. Vascular parameters including carotid intima-media thickness (cIMT) and endothelial function was analyzed by ecodoppler and periflux respectively.Results:The genome-wide methylation analysis identified 112 DMGs including 41 hypomethylated and 71 hypermethylated. These differentially methylated genes were enriched with several signaling pathways and disease categories including immune response, metabolic processes, oxidative stress, vascular and inflammatory pathways. The altered gene expression of selected genes with altered methylation levels in PsA was also validated. Correlation and association analysis of these DMGs with clinical and analytical variables, cardiovascular risk factors and endothelial microvascular function revealed that the degree of methylation of these genes was significantly associated with cIMT (IGF1R, NDRG3, SMYD3, HLA-DRB1, WDR70), arterial pressure (METT5D1, NRDG3, ADAM17, SMYD3, WNK1, CBX1), insulin resistance (AKAP13, SEMA6D, PLCB1), altered lipid profile and atherogenic index (MYBL1, METT5D1, MAN2A1, SLC1A7, SEMA6D, PLCB1, TLK1, SDK1, CBX1), inflammation (MYBL1, NDUFA5, METT5D1, SEMA6D, PLCB1, TLK1), and endothelial dysfunction (ADAMST10, GPCPD1, CCDC88A). In addition, this analysis also identified 435 DMGs including 280 hypomethylated and 155 hypermethylated in CD4+T cells from IR-PsA vs non IR-PsA patients. Between these two groups of PsA patients, CHUK, SERINC1, RUNX1, TTYH2, TXNDC11, FAF1, BICD1, SCD5, PDE5A, FAS, NFIA and GRP75 displayed the most significantly altered methylation, suggesting the role of these genes in the metabolic complications associated with PsA.Conclusion:These findings help our understanding of the pathogenesis of PsA and advance epigenetic studies in regards to this disease and the cardiometabolic comorbidities associated. Funded by ISCIII (PI17/01316 and RIER RD16/0012/0015) co-funded with FEDER.Disclosure of Interests:Iván Arias de la Rosa: None declared, María Dolores López Montilla Speakers bureau: Celgene, Javier Rodríguez: None declared, Esteban Ballester: None declared, Carmen Torres-Granados: None declared, Carlos Perez-Sanchez: None declared, Maria del Carmen Abalos-Aguilera: None declared, Gómez García Ignacio: None declared, Desiree Ruiz: None declared, Alejandra M. Patiño-Trives: None declared, María Luque-Tévar: None declared, Eduardo Collantes-Estévez Grant/research support from: ROCHE and Pfizer., Speakers bureau: ROCHE, Lilly, Bristol and Celgene., Chary Lopez-Pedrera Grant/research support from: ROCHE and Pfizer., Alejandro Escudero Contreras Grant/research support from: ROCHE and Pfizer, Speakers bureau: ROCHE, Lilly, Bristol and Celgene., Nuria Barbarroja Puerto Grant/research support from: ROCHE and Pfizer., Speakers bureau: ROCHE and Celgene.

scholarly journals Aberrant DNA methylation involved in obese women with systemic insulin resistance

2018 ◽  
Vol 13 (1) ◽  
pp. 201-207 ◽  
Author(s):  
Shao-Jun Zhang ◽  
Yan Wang ◽  
Yan-Lan Yang ◽  
Hong Zheng
Keyword(s):  
Insulin Resistance ◽  
Dna Methylation ◽  
Dermatan Sulfate ◽  
Gene Expression Omnibus ◽  
Obese Women ◽  
Disease Etiology ◽  
Insulin Resistant ◽  
Epigenetic Biomarkers ◽  
Systemic Insulin Resistance ◽  
Differentially Methylated Genes

AbstractBackgroundEpigenetics has been recognized as a significant regulator in many diseases. White adipose tissue (WAT) epigenetic dysregulation is associated with systemic insulin resistance (IR). The aim of this study was to survey the differential methylation of genes in obese women with systemic insulin resistance by DNA methylation microarray.MethodsThe genome-wide methylation profile of systemic insulin resistant obese women was obtained from Gene Expression Omnibus database. After data preprocessing, differing methylation patterns between insulin resistant and sensitive obese women were identified by Student’s t-test and methylation value differences. Network analysis was then performed to reveal co-regulated genes of differentially methylated genes. Functional analysis was also implemented to reveal the underlying biological processes related to systemic insulin resistance in obese women.ResultsRelative to insulin sensitive obese women, we initially screened 10,874 differentially methylated CpGs, including 7402 hyper-methylated sites and 6073 hypo-methylated CpGs. Our analysis identified 4 significantly differentially methylated genes, including SMYD3, UST, BCL11A, and BAI3. Network and functional analyses found that these differentially methylated genes were mainly involved in chondroitin and dermatan sulfate biosynthetic processes.ConclusionBased on our study, we propose several epigenetic biomarkers that may be related to obesity-associated insulin resistance. Our results provide new insights into the epigenetic regulation of disease etiology and also identify novel targets for insulin resistance treatment in obese women.

THU0381 MANAGEMENT OF CARDIOVASCULAR COMORBIDITY IN PSORIATIC ARTHRITIS IN THE ROUTINE CLINICAL PRACTICE: A COMPARATIVE STUDY OF METHOTREXATE OR APREMILAST AS MONOTHERAPY AND COMBINED

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 424-425
Author(s):  
N. Barbarroja Puerto ◽  
I. Arias de la Rosa ◽  
C. Torres-Granados ◽  
M. D. C. Abalos-Aguilera ◽  
G. G. Ignacio ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Disease Activity ◽  
Lipid Profile ◽  
Combined Therapy ◽  
Routine Clinical Practice ◽  
Research Support ◽  
Number Of Patients

Background:The presence of cardiovascular disease in psoriatic arthritis (PsA) is of particular concern, as it is considered the leading cause of mortality in PsA. Thus, it is essential to recognize those appropriate therapies that could target this comorbidity, reducing the risk of cardiovascular disease and metabolic alterations.Objectives:To evaluate the efficacy of methotrexate (MTX) and apremilast as monotherapies or in combination, in the clinical manifestations of the disease and the reduction of cardiovascular risk factors in PsA.Methods:Prospective longitudinal study in 30 PsA patients diagnosed according to CASPAR criteria: 10 patients were treated with MTX (12 ± 2,58 mg/week), 10 patients with apremilast (60 mg/day) and 10 were treated with combined therapy for 6 months, recruited in the routine clinical practice at the Reina Sofia Hospital of Cordoba and University Hospital of Jaen, Spain. Clinical and analytical parameters were collected at baseline and after 6 months of treatment: lipid profile (cholesterol, HDL, LDL, TG, ApoA and ApoB), glucose and insulin, body surface area (BSA) affected by psoriasis, number of tender and swollen joints, DAS28, DAPSA, VAS, CRP and ESR.The presence of cardiometabolic risk factors such as metabolic syndrome (MetSyn) was evaluated according to National Cholesterol Education Program (NCEP) adult treatment panel III (ATP III) criteria, meeting 3 of the following characteristics: abdominal obesity (men (>102 cm); women (>88 cm), TG > 150 mg/dL, HDL (men (<40 mg/dL); women (<50 mg/dL), blood pressure > 130/85 mmHg, glucose levels > 110 mg/dL). Insulin resistance (HOMA-IR > 2,5), body mass index (BMI), ApoB/ApoA ratio, atherogenic index (AI) and SCORE (age, gender, cholesterol, HDL, smoking habit and diabetes) were also studied.Results:Apremilast or MTX monotherapies caused a moderate reduction of the clinical inflammatory markers (CRP and ESR) and disease activity (VAS, DAPSA and DAS28) after 6 months of treatment. On the other hand, while apremilast significantly reduced the affected BSA, MTX had no significant effect. All those parameters were more significantly reduced after the combined treatment (MTX+ apremilast).Apremilast monotherapy significantly improved alterations in the lipid profile (reducing cholesterol and LDL levels, ApoB/ApoA ratio and AI), insulin resistance and decreased BMI, thus reducing the number of patients with MetSyn. MTX monotherapy treatment had no positive effect on these parameters. None of the treatments had significant effects on SCORE values.The beneficial effects of apremilast on the lipid profile were mitigated after the combination with MTX. Nevertheless, the number of patients with MetSyn decreased even more after the combined therapy of MTX with apremilast compared to apremilast monotherapy.Conclusion:1) In patients with moderate disease activity, treatment with apremilast monotherapy might have some advantages compared to the MTX monotherapy, since it can decrease the percentage of BSA with psoriasis, the lipid profile alteration, IR and weight, thus improving the cardiovascular risk profile. 2) Combined therapy (MTX+ apremilast) can induce a deeper reduction in the disease activity compared to the monotherapies, maintaining, in turn, the positive effects of apremilast on the cardiovascular risk.Funded by ISCIII (PI17/01316 and RIER RD16/0012/0015) co-funded with FEDER.Disclosure of Interests:Nuria Barbarroja Puerto Grant/research support from: ROCHE and Pfizer., Speakers bureau: ROCHE and Celgene., Iván Arias de la Rosa: None declared, Carmen Torres-Granados: None declared, Maria del Carmen Abalos-Aguilera: None declared, Gómez García Ignacio: None declared, Isabel Añón Oñate: None declared, María José Pérez Galán: None declared, Desiree Ruiz: None declared, Alejandra M. Patiño-Trives: None declared, María Luque-Tévar: None declared, Eduardo Collantes Estevez Grant/research support from: ROCHE and Pfizer, Speakers bureau: ROCHE, Lilly, Bristol and Celgene, Chary Lopez-Pedrera Grant/research support from: ROCHE and Pfizer., Alejandro Escudero Contreras Grant/research support from: ROCHE and Pfizer, Speakers bureau: ROCHE, Lilly, Bristol and Celgene., María Dolores López Montilla Speakers bureau: Celgene

scholarly journals O11 Lymphocyte DNA methylation mediates genetic risk at RA risk loci that are shared with other immune mediated diseases

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Alexander D Clark ◽  
Nisha Nair ◽  
Amy E Anderson ◽  
Nishanthi Thalayasingam ◽  
Najib Naamane ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
T Cells ◽  
B Cells ◽  
Quantitative Trait ◽  
Genetic Risk ◽  
Early Arthritis ◽  
Site Specific ◽  
Genome Wide ◽  
Immune Mediated

Abstract Background The aetiology of rheumatoid arthritis (RA) is complex. In particular, the vast majority of disease-associated variants implicated by genome-wide association studies are non-coding, leaving genetic mechanisms of adaptive immune dysregulation unresolved. The contribution to this process of epigenetic factors, including the addition of methyl groups to DNA, also remains uncertain. To address these issues and prioritise causal genes for downstream study, genome-wide data incorporating DNA methylation and gene expression measurements from lymphocyte subsets in an early arthritis inception cohort, were available. Methods Whole genome methylation and transcription data from isolated CD4+ T cells and B cells of &gt; 100 well-characterised inflammatory arthritis patients, all of whom were naïve to immunomodulatory treatments and of Northern European ancestry, were obtained (Illumina HumanHT-12 v4 Expression BeadChip and Infinium MethylationEPIC BeadChip arrays, respectively). Genotyping was undertaken using the Illumina Human CoreExome-24 version 1-0 array. After independent pre-processing, normalisation and quality control of paired CD4+ and B lymphocyte data, methylation quantitative trait loci (meQTLs) were first modelled using the MatrixEQTL package in each cell type. Next, at RA risk-associated cis-CpGs, correlations between site-specific methylation and the expression of genes within ±500Kb identified quantitative trait methylations (eQTMs). To infer directionality of SNP-CpG-transcript associations a causal inference test (CIT) was applied. Multiple testing was accounted for, and in vitro assays were used to validate meQTLs at loci of interest and confirm regulatory mechanisms. Further analysis integrated GWAS data from other immune mediated diseases (IMDs) and additional publically available resources. Results We found strong evidence that disease-associated DNA variants regulate cis-CpG methylation of DNA in CD4+ T and/or B cells at 37% RA loci. In general we observed these variants to preferentially modify methylation at sites mapping to lymphocyte enhancers and regions flanking transcription start sites, and at positions bound by the NFκB transcription factor. Using paired, cell-specific transcriptomic data and a statistical approach to infer causality, we then identified examples where site-specific DNA methylation in turn mediates gene expression, including ORMDL3/GSDMB, IL6ST/ANKRD55, FCRL3 and JAZF1 in CD4+ lymphocytes. Leveraging GWAS data we noted that a number of genes regulated in this way highlight mechanisms common to RA, multiple sclerosis and asthma, distinguishing these IMDs from osteoarthritis which is considered a primarily degenerative disease. To validate our findings, cis-meQTL effects at sentinel loci were replicated by pyrosequencing in an independent cohort of genotyped early arthritis patients, and methylation-mediated regulation of FCRL3 expression downstream of the regulatory SNP was confirmed experimentally using a luciferase reporter assay in Jurkat T-cells. Conclusion Our observations highlight important mechanisms of genetic risk in RA and the wider context of autoimmunity. They confirm the utility of DNA methylation profiling as a tool for causal gene prioritisation and, potentially, therapeutic targeting in complex IMD. Disclosures A.D. Clark None. N. Nair None. A.E. Anderson None. N. Thalayasingam None. N. Naamane None. A.J. Skelton None. J. Diboll None. A. Barton None. S. Eyre None. J.D. Isaacs None. L.N. Reynard None. A.G. Pratt Grants/research support; I am a recipient of an unrestricted, investigator initiated research grant from Pfizer, paid to Newcastle University.

scholarly journals FRI0052 INFLUENCE OF RHEUMATOID ARTHRITIS ON THE CLINICAL AND BIOLOGICAL PROFILE OF TYPE-2 DIABETES MELLITUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 601.2-602
Author(s):  
J. Avouac ◽  
M. Elhai ◽  
M. Forien ◽  
J. Sellam ◽  
F. Eymard ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Requirement ◽  
Multivariate Logistic Regression ◽  
Biological Profile ◽  
Research Support ◽  
Insulin Resistant ◽  
Research Grant

Background:Type-2 diabetes and rheumatoid arthritis (RA) are two chronic diseases characterized by tissue inflammation and insulin resistance. To date, no data have evaluated the influence of RA-induced joint and systemic inflammation on the course of type-2 diabetes.Objectives:To study the impact of RA on type-2 diabetesMethods:Observational, multicenter, cross-sectional usual-care study, including 7 rheumatology centers. This study included over a 24-month period consecutive patients with type-2 diabetes and RA, fulfilling the 2010 ACR / EULAR criteria, and diabetic controls with osteoarthritis (OA). The following data were collected: demographics, disease activity and severity indices, current treatment for RA and diabetes, history and complications of diabetes. A systematic blood test was performed, assessing inflammatory (CRP levels) and metabolic (fasting glycemia and insulin levels, HbA1c) parameters. The HOMA2%B (insulin secretion) and HOMA2%S (tissue insulin sensitivity) indices (HOMA calculator, © Diabetes Trials Unit, University of Oxford) were used to assess insulin resistance. Ra and OA patients were compared using parametric tests after adjusting for age and BMI. A multivariate logistic regression was performed ti identify factors independently associated with insulin resistance.Results:We included 122 RA patients (74% women, mean age 64+/-11 years, mean disease duration 15+/-11 11 years, 75% with positive ACPA antibodies and 64% with erosive disease) and 54 controls with OA. 64% of RA patients were treated with oral corticosteroids <10 mg/day, 65% received methotrexate and 53% received targeted biological therapies.The characteristics of type-2 diabetes in the 54 OA patients corresponded to severe insulin-resistant diabetes: age> 65 years, high BMI> 30 kg/m2, mean HbA1c 7.3%+/-11 1.3%, 30% of insulin requirement, high frequency of other cardiovascular risk factors, macroangiopathy found in almost half of patients and biological criteria of insulin resistance (elevation of HOMA2%B and decrease of HOMA2%S).RA patients with type-2 diabetes had a younger age (64+/-11 years vs. 68+/-12 years, p=0.031) and lower BMI (27.7+/-11 5.5 vs. 31.5+/-11 6.3, p<0.001). These patients also had severe diabetes (HbA1c 7.0%+/-11 1.2%, 29% of insulin requirement, 43% of macroangiopathy) with an insulin resistance profile identical to OA controls. After adjusting for age and BMI, RA patients had a significantly increased insulin secretion compared to OA patients (HOMA2%B: 83.1+/-11 65.2 vs. 49.3+/-11 25.7, p=0.023) as well as a significant reduction of insulin sensitivity (HOMA2%S: 61.1+/-11 31.6 vs. 92.9+/-11 68.1, p=0.016). This insulin resistance was associated with the inflammatory activity of RA, with a negative correlation between the HOMA2%S and the DAS28 (r=-0.28, p=0.027). The multivariate logistic regression confirmed the independent association between the HOMA2%S index and DAS28 (OR: 3.93, 95% CI 1.02-15.06), as well as high blood pressure (OR: 1.29, 95% CI 0.33-1.99 CI).Conclusion:RA patients with type-2 diabetes displayed severe, poorly controlled diabetes, highlighting the burden of comorbidities associated with RA. The clinical-biological profile of diabetic RA patients was severe insulin-resistant diabetes, with a biological profile of insulin resistance linked to the inflammatory activity of the disease. These findings may have therapeutic implications, with the potential targeting of insulin resistance through the treatment of joint and systemic inflammation.Acknowledgments:Société Française de Rhumatologie (research grant)Bristol Myers Squibb (research grant)Disclosure of Interests:Jérôme Avouac Grant/research support from: Pfizer, Bristol Myers Squibb, Consultant of: Sanofi, Bristol Myers Squibb, Abbvie, Boerhinger, Nordic Pharma, Speakers bureau: Sanofi, Bristol Myers Squibb Abbvie, MSD, Pfizer, Nordic Pharma, Muriel ELHAI: None declared, Marine Forien: None declared, Jérémie SELLAM: None declared, Florent Eymard Consultant of: Regenlab, Anna Moltó Grant/research support from: Pfizer, UCB, Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, UCB, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Frédéric Banal: None declared, Joel Daminano: None declared, Philippe Dieudé: None declared, Yannick Allanore Shareholder of: Sanofi, Roche, Consultant of: Actelion, Bayer, BMS, Boehringer Ingelheim, Inventiva, Sanofi

scholarly journals Meta-analysis of epigenome-wide association studies of carotid intima-media thickness

2021 ◽  
Author(s):  
Eliana Portilla-Fernández ◽  
Shih-Jen Hwang ◽  
Rory Wilson ◽  
Jane Maddock ◽  
W. David Hill ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Association Studies ◽  
Subclinical Atherosclerosis ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Media Thickness

AbstractCommon carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = −0.0264, p value = 3.5 × 10–8) in the discovery panel and was replicated in replication panel (beta = −0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

scholarly journals A Genome-Wide Integrative Association Study of DNA Methylation and Gene Expression Data and Later Life Cognitive Functioning in Monozygotic Twins

2020 ◽  
Vol 14 ◽  
Author(s):  
Mette Soerensen ◽  
Dominika Marzena Hozakowska-Roszkowska ◽  
Marianne Nygaard ◽  
Martin J. Larsen ◽  
Veit Schwämmle ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cognitive Functioning ◽  
Association Study ◽  
Gene Expression Data ◽  
Monozygotic Twins ◽  
Later Life ◽  
Expression Data ◽  
Genome Wide ◽  
A Genome

Investigation of the prevalence of cardiovascular risk factors in obese patients diagnosed with metabolic syndrome in childhood and examination of left ventricular function by echocardiography

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Güzin Özden ◽  
Ayşe Esin Kibar Gül ◽  
Eda Mengen ◽  
Ahmet Ucaktürk ◽  
Hazım Alper Gürsu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Left Ventricular ◽  
Atherogenic Index ◽  
Volume Index ◽  
Common Component

Abstract Objectives The objective of this study is to investigate the cardiovascular risk factors associated with metabolic syndrome (MetS), which is increasingly becoming prevalent in childhood obesity. Methods A total of 113 patients, 76 of whom were between the ages of 10 and 17 (mean age: 14.5 ± 1.8 years) and diagnosed with obesity (30 non-MetS and 46 MetS using IDF) and 37 of whom constituted the control group, participated in the study. Echocardiographic examination and atherogenicity parameters (Atherogenic index of plasma [AIP: logTG/HDL], total cholesterol/HDL, and TG/HDL ratio and non-HDL) were evaluated. Results The most common component accompanying obese MetS was found to be hypertension and low HDL. While obesity duration, body mass index (BMI), blood pressure, fasting insulin, insulin resistance, atherogenicity parameters were determined to be significantly higher in the obese-MetS group. Echocardiography showed that while the thickness, volume, and diameter of LV end-diastolic wall, left ventricular mass (LVM), LVM index (LVMI g/m2) and relative wall thickness (RWT) were significantly high in the MetS group, however, mitral E/A ratio was significantly lower (p<0.05). Change in LV geometry consistent with concentric remodeling (increased RWT, normal LVMI) was visible in obese groups. LVM were positively significantly related to BMI, waist circumference, insulin resistance, blood pressure, LDL level, and negative to mitral E/A ratio. In the obese-MetS group, LVMI was positively correlated to office systolic BP, left atrium end-diastolic volume/index. Conclusions LVMI and atherogenicity parameters that were found to be significantly higher in obese MetS exhibit increased cardiovascular risk in childhood.

scholarly journals Cellular Heterogeneity–Adjusted cLonal Methylation (CHALM) improves prediction of gene expression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianfeng Xu ◽  
Jiejun Shi ◽  
Xiaodong Cui ◽  
Ya Cui ◽  
Jingyi Jessica Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cellular Heterogeneity ◽  
Biological Functions ◽  
Global Correlation ◽  
Differentially Methylated Genes ◽  
Promoter Dna Methylation ◽  
Functional Consequences ◽  
Promoter Dna ◽  
Underlying Mechanisms

AbstractPromoter DNA methylation is a well-established mechanism of transcription repression, though its global correlation with gene expression is weak. This weak correlation can be attributed to the failure of current methylation quantification methods to consider the heterogeneity among sequenced bulk cells. Here, we introduce Cell Heterogeneity–Adjusted cLonal Methylation (CHALM) as a methylation quantification method. CHALM improves understanding of the functional consequences of DNA methylation, including its correlations with gene expression and H3K4me3. When applied to different methylation datasets, the CHALM method enables detection of differentially methylated genes that exhibit distinct biological functions supporting underlying mechanisms.

scholarly journals The impact of obesity on cardiovascular disease risk factor

2018 ◽  
Vol 10 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Arun Kumar
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Cardiovascular Risk ◽  
Sodium Intake ◽  
Action Plan ◽  
Saturated Fat ◽  
The World

Obesity has emerged as the most potential cardiovascular risk factor and has raised concern among public and their health related issues not only in developed but also in developing countries. The Worldwide obesity occurrence has almost has gone three times since 1975. Research suggests there are about 775 million obese people in the World including adult, children, and adolescents. Nearly 50% of the children who are obese and overweight in Asia in are below 5 years. There is a steep incline of childhood obesity when compared to 1971 which is not only in developed countries but also in developing countries. A considerable amount of weight gain occurs during the transition phase from adolescence to young adulthood. It is also suggested that those adultswho were obese in childhood also remained obese in their adulthood with a higher metabolic risk than those who became obese in their adulthood. In India, the urban Indian female in the age group of 30-45 years have emerged as an 〝at risk population” for cardiovascular diseases. To understand how obesity can influence cardiovascular function, it becomes immense important to understand the changes which can take place in adipose tissue due to obesity. There are two proposed concepts explaining the inflammatory status of macrophage. The predominant cause of insulin resistance is obesity. Epidemiological and research studies have indicated that the pathogenesis of obesity-related metabolic dysfunction involves the development of a systemic, low-grade inflammatory state. It is becoming clear that targeting the pro-inflammatory pathwaymay provide a novel therapeutic approach to prevent insulin resistance, particularly in obesity inducedinsulin resistance. Some cost effective interventions that are feasible by all and can be implemented even in low-resource settings includes - population-wide and individual, which are recommended to be used in combination to reduce the greatest cardiovascular disease burden. The sixth target in the Global NCD action plan is to reduce the prevalence of hypertension by 25%. Reducing the incidence of hypertension by implementing population-wide policies to educe behavioral risk factors. Reducing cigarette smoking, body weight, blood pressure, blood cholesterol, and blood glucose all have a beneficial impact on major biological cardiovascular risk factors. A variety of lifestyle modifications have been shown, in clinical trials, to lower bloodpressure, includes weight loss, physical activity, moderation of alcohol intake, increased fresh fruit and vegetables and reduced saturated fat in the diet, reduction of dietary sodium intake, andincreased potassium intake. Also, trials of reduction of saturated fat and its partial replacement by unsaturated fats have improved dyslipidaemia and lowered risk of cardiovascular events. This initiative driven by the Ministry of Health and Family Welfare, State Governments, Indian Council of Medical Research and the World Health Organization are remarkable. The Government of India has adopted a national action plan for the prevention and control of non-communicable diseases (NCDs) with specific targets to be achieved by 2025, including a 25% reduction inoverall mortality from cardiovascular diseases, a 25% relative reduction in the prevalence of raised blood pressure and a 30% reduction in salt/sodium intake. In a nutshell increased BMI values can predict the nature of obesity and its aftermaths in terms inflammation and other disease associated with obesity. It’s high time; we must realize it and keep an eye on health status in order to live long and healthy life.

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