scholarly journals Epigenetic silencing of the ANKRD26 gene correlates to the pro-inflammatory profile and increased cardio-metabolic risk factors in human obesity

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Antonella Desiderio ◽  
Michele Longo ◽  
Luca Parrillo ◽  
Michele Campitelli ◽  
Giuseppe Cacace ◽  
...  

Abstract Background Obesity is a major worldwide threat to human health. Increasing evidence indicates that epigenetic modifications have a major impact on the natural history of this disorder. Ankyrin Repeat Domain 26 (Ankrd26) is involved in the development of both obesity and diabetes in mice and is modulated by environmentally induced epigenetic modifications. This study aims at investigating whether impaired ANKRD26 gene expression and methylation occur in human obesity and whether they correlate to the phenotype of these subjects. Results We found that downregulation of ANKRD26 mRNA and hyper-methylation of a specific region of the ANKRD26 promoter, embedding the CpG dinucleotides − 689, − 659, and − 651 bp, occur in peripheral blood leukocytes from obese compared with the lean subjects. ANKRD26 gene expression correlates inversely to the percentage of DNA methylation at these 3 CpG sites. Luciferase assays reveal a cause-effect relationship between DNA methylation at the 3 CpG sites and ANKRD26 gene expression. Finally, both ANKRD26 mRNA levels and CpG methylation correlate to body mass index and to the pro-inflammatory status and the increased cardio-metabolic risk factors of these same subjects. Conclusion Downregulation of the ANKRD26 gene and hyper-methylation at specific CpGs of its promoter are common abnormalities in obese patients. These changes correlate to the pro-inflammatory profile and the cardio-metabolic risk factors of the obese individuals, indicating that, in humans, they mark adverse health outcomes.

PLoS ONE ◽  
2010 ◽  
Vol 5 (9) ◽  
pp. e12609 ◽  
Author(s):  
Tuija Leskinen ◽  
Rita Rinnankoski-Tuikka ◽  
Mirva Rintala ◽  
Tuulikki Seppänen-Laakso ◽  
Eija Pöllänen ◽  
...  

2015 ◽  
Vol 399 ◽  
pp. 87-94 ◽  
Author(s):  
Sadashiv ◽  
Sunita Tiwari ◽  
Vani Gupta ◽  
Bhola Nath Paul ◽  
Sandeep Kumar ◽  
...  

2006 ◽  
Vol 16 (6) ◽  
pp. 745-751 ◽  
Author(s):  
Rosa Morínigo ◽  
Melina Musri ◽  
Josep Vidal ◽  
Roser Casamitjana ◽  
Salvadora Delgado ◽  
...  

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243600
Author(s):  
Bahram Moazzami ◽  
Shahla Chaichian ◽  
Amir Kasaeian ◽  
Shirin Djalalinia ◽  
Meisam Akhlaghdoust ◽  
...  

Objective Based on the epidemiologic findings of Covid-19 incidence; illness and mortality seem to be associated with metabolic risk factors. This systematic review and meta-analysis aimed to assess the association of metabolic risk factors and risk of Covid-19. Methods This study was designed according to PRISMA guidelines. Two independent researchers searched for the relevant studies using PubMed, Web of Science, Cochrane Library, and Scopus. The search terms developed focusing on two main roots of “Covid-19” and “metabolic risk factors”. All relevant observational, analytical studies, review articles, and a meta-analysis on the adult population were included in this meta-analysis. Meta-analysis was performed using the random effect model for pooling proportions to address heterogeneity among studies. Data were analyzed using STATA package version 11.2, (StataCorp, USA). Results Through a comprehensive systematic search in the targeted databases we found 1124 papers, after running the proses of refining, 13 studies were included in the present meta-analysis. The pooled prevalence of obesity in Covid-19 patients was 29% (95% CI: 14–47%). For Diabetes and Hypertension, these were 22% (95% CI: 12% 33%) and 32% (95% CI: 12% 56%), respectively. There was significant heterogeneity in the estimates of the three pooled prevalence without any significant small-study effects. Such warning points, to some extent, guide physicians and clinicians to better understand the importance of controlling co-morbid risk factors in prioritizing resource allocation and interventions. Conclusion The meta-analysis showed that hypertension is more prevalent than obesity and diabetes in patients with Covid-19 disease. The prevalence of co-morbid metabolic risk factors must be adopted for better management and priority settings of public health vaccination and other required interventions. The results may help to improve services delivery in COVID-19 patients, while helping to develop better policies for prevention and response to COVID-19 and its critical outcomes.


2009 ◽  
Vol 19 (3) ◽  
pp. 177-183 ◽  
Author(s):  
M. Hietaniemi ◽  
M. Jokela ◽  
M. Rantala ◽  
O. Ukkola ◽  
J.T. Vuoristo ◽  
...  

2019 ◽  
Vol 48 (3) ◽  
pp. 887-898 ◽  
Author(s):  
Tom G Richardson ◽  
Rebecca C Richmond ◽  
Teri-Louise North ◽  
Gibran Hemani ◽  
George Davey Smith ◽  
...  

Abstract Background There is mounting evidence that our environment and lifestyle has an impact on epigenetic regulatory mechanisms, such as DNA methylation. It has been suggested that these molecular processes may mediate the effect of risk factors on disease susceptibility, although evidence in this regard has been challenging to uncover. Using genetic variants as surrogate variables, we have used two-sample Mendelian randomization (2SMR) to investigate the potential implications of putative changes to DNA methylation levels on disease susceptibility. Methods To illustrate our approach, we identified 412 CpG sites where DNA methylation was associated with prenatal smoking. We then applied 2SMR to investigate potential downstream effects of these putative changes on 643 complex traits using findings from large-scale genome-wide association studies. To strengthen evidence of mediatory mechanisms, we used multiple-trait colocalization to assess whether DNA methylation, nearby gene expression and complex trait variation were all influenced by the same causal genetic variant. Results We identified 22 associations that survived multiple testing (P < 1.89 × 10–7). In-depth follow-up analyses of particular note suggested that the associations between DNA methylation at the ASPSCR1 and REST/POL2RB gene regions, both linked with reduced lung function, may be mediated by changes in gene expression. We validated associations between DNA methylation and traits using independent samples from different stages across the life course. Conclusion Our approach should prove valuable in prioritizing CpG sites that may mediate the effect of causal risk factors on disease. In-depth evaluations of findings are necessary to robustly disentangle causality from alternative explanations such as horizontal pleiotropy.


Sign in / Sign up

Export Citation Format

Share Document