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DNA methylation signature connects chronic inflammation and diseases
The researchers developed a clinically applicable risk score associated with weight, BMI, type 2 diabetes, coronary disease, and several other inflammation markers.
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Low-grade inflammation triggers the development of multiple chronic conditions, including type 2 diabetes, cardiovascular disease, chronic obstructive pulmonary disease, as well as several psychological disorders. C-reactive protein (CRP) is commonly used as a marker for chronic low-grade inflammation. Existing studies established a strong connection between elevated serum CRP and genetics, obesity, physical inactivity, fiber intake, and smoking. But the molecular mechanisms behind this association are not well understood.
The key mechanism to understanding this link might be DNA methylation (an epigenetic modification such as the reversible addition of a methyl group to a cytosine base in DNA). Understanding how exactly gene expression patterns are affected by methylation under various factors (excess adiposity or smoking) in relation to chronic inflammation could highlight pathways to counteract these changes.
To investigate a complex network of epigenetic alterations, Wielscher et al. performed one of the largest multi-ethnic epigenome-wide association studies (EWAS) on serum CRP in more than 22 thousand participants. Participants were subdivided into groups of African American and African ancestries, European ancestry, and South Asian ancestry.
The researchers found a total of 1765 markers significantly associated with serum CRP levels. Though 62 markers were specific to European ancestry and 2 to South Asian ancestry only, no statistically significant heterogeneity was detected otherwise.
Further, the study analyzed the causal role of DNA methylation. Previously, it has been shown that BMI and Crohn’s disease cause DNA methylation changes. However, only in this study the researchers confirm that this causal pathway occurs through low-grade inflammation, mediated by CRP. The detailed analysis allowed identifying the relevant loci (places on the DNA) responsible for the disease-inducing changes.
Based on the complex data of detected DNA methylation signature, the researchers developed a clinically applicable risk score associated with weight, BMI, several other inflammation markers (interleukin 6 and tumor necrosis factor), type 2 diabetes, coronary disease, and hypertension. Since DNA methylation is a reversible process, such implementation of low-grade inflammation-associated methylation signatures can be easily employed as a tool to monitor the progress of beneficial lifestyle changes. In a healthy population, this signature can be applied as a warning proxy for chronic inflammation development.
Source Nature Communications
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Low-grade inflammation triggers the development of multiple chronic conditions, including type 2 diabetes, cardiovascular disease, chronic obstructive pulmonary disease, as well as several psychological disorders. C-reactive protein (CRP) is commonly used as a marker for chronic low-grade inflammation. Existing studies established a strong connection between elevated serum CRP and genetics, obesity, physical inactivity, fiber intake, and smoking. But the molecular mechanisms behind this association are not well understood.
The key mechanism to understanding this link might be DNA methylation (an epigenetic modification such as the reversible addition of a methyl group to a cytosine base in DNA). Understanding how exactly gene expression patterns are affected by methylation under various factors (excess adiposity or smoking) in relation to chronic inflammation could highlight pathways to counteract these changes.
To investigate a complex network of epigenetic alterations, Wielscher et al. performed one of the largest multi-ethnic epigenome-wide association studies (EWAS) on serum CRP in more than 22 thousand participants. Participants were subdivided into groups of African American and African ancestries, European ancestry, and South Asian ancestry.
The researchers found a total of 1765 markers significantly associated with serum CRP levels. Though 62 markers were specific to European ancestry and 2 to South Asian ancestry only, no statistically significant heterogeneity was detected otherwise.
Further, the study analyzed the causal role of DNA methylation. Previously, it has been shown that BMI and Crohn’s disease cause DNA methylation changes. However, only in this study the researchers confirm that this causal pathway occurs through low-grade inflammation, mediated by CRP. The detailed analysis allowed identifying the relevant loci (places on the DNA) responsible for the disease-inducing changes.
Based on the complex data of detected DNA methylation signature, the researchers developed a clinically applicable risk score associated with weight, BMI, several other inflammation markers (interleukin 6 and tumor necrosis factor), type 2 diabetes, coronary disease, and hypertension. Since DNA methylation is a reversible process, such implementation of low-grade inflammation-associated methylation signatures can be easily employed as a tool to monitor the progress of beneficial lifestyle changes. In a healthy population, this signature can be applied as a warning proxy for chronic inflammation development.
Source Nature Communications
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Dr. Ana Baroni MD. Ph.D.
Scientific & Medical Advisor
Quality Garant
Ana has over 20 years of consultancy experience in longevity, regenerative and precision medicine. She has a multifaceted understanding of genomics, molecular biology, clinical biochemistry, nutrition, aging markers, hormones and physical training. This background allows her to bridge the gap between longevity basic sciences and evidence-based real interventions, putting them into the clinic, to enhance the healthy aging of people. She is co-founder of Origen.life, and Longevityzone. Board member at Breath of Health, BioOx and American Board of Clinical Nutrition. She is Director of International Medical Education of the American College of Integrative Medicine, Professor in IL3 Master of Longevity at Barcelona University and Professor of Nutrigenomics in Nutrition Grade in UNIR University.
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