EPIGENETIC MODIFICATIONS ASSOCIATED WITH DYSLIPIDEMIA AMONG OBESE CHILDREN AND ADOLESCENTS

Abstract

BackgroundThe mechanisms why certain obese adolescents are more susceptible to developing dyslipidemia are not completely understood. Epigenetic elements, such as DNA methylation, may play a significant role in lipid traits.MethodsWe studied a prospectively enrolled cohort of overweight and obese children and adolescents recruited from obesity-related clinics at the Boston Children’s Hospital with body composition measures (air displacement plethysmograph) and fasting cholesterol samples. A nested case-control pilot study was conducted and 12 participants were selected based on extremes of obesity-related lipid traits. Whole blood DNA methylation was interrogated using the Illumina HumanMethylation450 microarray with normalization and adjustment for cell-count. Age and sex adjusted multiple linear regression models were run assessing HDL-C, triglycerides, and case-control status, controlled for multiple testing. Primary models assessed DNA methylation within candidate loci and secondary analysis examined genome-wide sites.ResultsAmong the 12 participants, the 6 with the most abnormal obesity-related traits were slightly older (13 vs. 11 years) but had similar BMI (Z-score 2.3 vs. 2.2) and % body fat (39% vs. 38%). Among the candidate regions, triglycerides were associated with differential methylation at cg20809737, intronic to the fatty acid oxidation enzyme carnitine palmitoyltransferase 1A, CPT1A (p=0.006).ConclusionWe demonstrate an association between differential methylation of CPT1A and triglycerides in children, supporting similar findings from adult studies. Epigenetic mechanisms may confer increased susceptibility to developing obesity-related dyslipidemia via alterations in DNA methylation. BackgroundThe mechanisms why certain obese adolescents are more susceptible to developing dyslipidemia are not completely understood. Epigenetic elements, such as DNA methylation, may play a significant role in lipid traits. The mechanisms why certain obese adolescents are more susceptible to developing dyslipidemia are not completely understood. Epigenetic elements, such as DNA methylation, may play a significant role in lipid traits. MethodsWe studied a prospectively enrolled cohort of overweight and obese children and adolescents recruited from obesity-related clinics at the Boston Children’s Hospital with body composition measures (air displacement plethysmograph) and fasting cholesterol samples. A nested case-control pilot study was conducted and 12 participants were selected based on extremes of obesity-related lipid traits. Whole blood DNA methylation was interrogated using the Illumina HumanMethylation450 microarray with normalization and adjustment for cell-count. Age and sex adjusted multiple linear regression models were run assessing HDL-C, triglycerides, and case-control status, controlled for multiple testing. Primary models assessed DNA methylation within candidate loci and secondary analysis examined genome-wide sites. We studied a prospectively enrolled cohort of overweight and obese children and adolescents recruited from obesity-related clinics at the Boston Children’s Hospital with body composition measures (air displacement plethysmograph) and fasting cholesterol samples. A nested case-control pilot study was conducted and 12 participants were selected based on extremes of obesity-related lipid traits. Whole blood DNA methylation was interrogated using the Illumina HumanMethylation450 microarray with normalization and adjustment for cell-count. Age and sex adjusted multiple linear regression models were run assessing HDL-C, triglycerides, and case-control status, controlled for multiple testing. Primary models assessed DNA methylation within candidate loci and secondary analysis examined genome-wide sites. ResultsAmong the 12 participants, the 6 with the most abnormal obesity-related traits were slightly older (13 vs. 11 years) but had similar BMI (Z-score 2.3 vs. 2.2) and % body fat (39% vs. 38%). Among the candidate regions, triglycerides were associated with differential methylation at cg20809737, intronic to the fatty acid oxidation enzyme carnitine palmitoyltransferase 1A, CPT1A (p=0.006). Among the 12 participants, the 6 with the most abnormal obesity-related traits were slightly older (13 vs. 11 years) but had similar BMI (Z-score 2.3 vs. 2.2) and % body fat (39% vs. 38%). Among the candidate regions, triglycerides were associated with differential methylation at cg20809737, intronic to the fatty acid oxidation enzyme carnitine palmitoyltransferase 1A, CPT1A (p=0.006). ConclusionWe demonstrate an association between differential methylation of CPT1A and triglycerides in children, supporting similar findings from adult studies. Epigenetic mechanisms may confer increased susceptibility to developing obesity-related dyslipidemia via alterations in DNA methylation. We demonstrate an association between differential methylation of CPT1A and triglycerides in children, supporting similar findings from adult studies. Epigenetic mechanisms may confer increased susceptibility to developing obesity-related dyslipidemia via alterations in DNA methylation.