Is there a genetic cause underlying the epidemic of obesity and metabolic syndrome, particularly among African Americans? An interdisciplinary team led by Dr. Tomi Akinyemiju, associate professor of epidemiology at the University of Kentucky College of Public Health, investigated this question, and released their results in the publication “Epigenome-wide association study of metabolic syndrome in African-American adults,” appearing this month in Clinical Epigenetics. Co-authors include Dr. Donna K. Arnett, professor of epidemiology and dean of the UK College of Public Health.
[Photo: Dean Donna K. Arnett (left) and Dr. Tomi Akinyemiju]
The high prevalence of obesity among U.S. adults has resulted in significant increases in associated metabolic disorders such as diabetes, dyslipidemia, and high blood pressure. Together, these disorders constitute metabolic syndrome, a clinically defined condition highly prevalent among African-Americans. Identifying epigenetic alterations associated with metabolic syndrome may provide additional information regarding etiology beyond current evidence from genome-wide association studies.
Investigators gathered data on metabolic syndrome and DNA methylation by assessing 614 African Americans from the Hypertension Genetic Epidemiology Network (HyperGEN) study. Metabolic syndrome was defined using the joint harmonized criteria, and DNA methylation was assessed using the Illumina HumanMethylation450K Bead Chip assay on DNA extracted from buffy coat. Linear mixed effects regression models were used to examine the association between CpG methylation at > 450,000 CpG sites, and metabolic syndrome adjusted for study covariates. Replication using DNA from a separate sample of 69 African-Americans, as well as meta-analysis combining both cohorts, was conducted.
The investigators found two differentially methylated CpG sites in the IGF2BP1 gene on chromosome 17 (cg06638433; p value = 3.10 × 10– 7) and the ABCG1 gene on chromosome 21 (cg06500161; p value = 2.60 × 10– 8) were identified. Results for the ABCG1gene remained statistically significant in the replication dataset and meta-analysis.
In this study, metabolic syndrome was consistently associated with increased methylation in the ABCG1 gene in the discovery and replication datasets, a gene that encodes a protein in the ATP-binding cassette transporter family and is involved in intra- and extra-cellular signaling and lipid transport.
The authors conclude: “The high prevalence of metabolic syndrome among African Americans and the consistent associations between metabolic syndrome and many chronic diseases such as cancer highlight the need for future prospective confirmatory studies that may inform clinical strategies and interventions.”