The Influence of Body Mass Index on Global DNA Methylation Levels in Blood Leukocytes
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Introduction: Body Mass Index (BMI) is a relative measure of whether an individual’s weight is at a healthy level for their height. A higher BMI is associated with an increased risk of cancer and cardiovascular disease (CVD). However, the biologic mechanisms are not well understood. One proposed mechanism is through changes in global DNA methylation levels, particularly global DNA hypomethylation. Global DNA hypomethylation refers to lower levels of DNA methylation across the entire genome and hypermethylation refers to higher levels of DNA methylation across the entire genome. Changes in methylation levels can affect gene expression, genomic stability, and chromosomal structure. The methylation status of repetitive sequences in the DNA, such as LINE-1, is commonly used to represent a surrogate measure of global DNA methylation levels. Objectives: 1. Quantify and describe LINE-1 DNA methylation in leukocytes in a large sample of healthy volunteers. 2. Examine the relationship between BMI and LINE-1 DNA methylation levels. 3. Assess if sex is an effect modifier of the relationship between BMI and LINE-1 DNA methylation levels. Methods: A nested cross-sectional study was composed of 502 healthy volunteers between the ages of 20 and 50. Subjects completed a study questionnaire and provided blood samples for laboratory analyses. For each subject, DNA was isolated, underwent bisulfite conversion, and LINE-1 DNA methylation levels were measured by Polymerase Chain Reaction (PCR) High-Resolution Melting Curve analysis. For the main analysis, a multivariate linear regression model was used to examine the relationship between BMI and LINE-1 DNA methylation levels, while controlling for confounders. Results: LINE-1 DNA methylation was normally distributed with a mean of 84.52% and a standard deviation of 3.19%. BMI (normal, overweight, and obese categories) was not significantly associated with LINE-1 DNA methylation levels in the adjusted linear regression model (p=0.41) and the interaction term between BMI and sex was not significant (p=0.50). Conclusions: LINE-1 DNA methylation was measured with a high degree of reliability in a sample of healthy volunteers. This research provided a description of LINE-1 DNA methylation levels in a large healthy population and showed that BMI was not associated with global DNA methylation.