Abstract 4243: Epigenome-wide association study of metabolic syndrome in African-Americans

Abstract

Abstract Background: The epidemic of obesity among US 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, including DNA methylation changes may provide information on biological pathways that are dysregulated and may potentially act as early biomarkers in cancer. Methods: Data on cardio-metabolic risk factors and DNA methylation was assessed on 606 African-Americans from the Hypertension Genetic Epidemiology Network (HyperGEN) study. Metabolic syndrome was defined using the joint harmonized criteria of at least three of: elevated waist circumference, high triglycerides, low HDL-cholesterol, high fasting blood glucose and high blood pressure. DNA methylation was assessed using the Illumina HumanMethylation 450K Bead Chip assay on DNA extracted from buffy coat. Linear mixed effects regression models were used to examine the association between CpG methylation and metabolic syndrome in crude and adjusted (for age, alcohol, smoking, sex) analyses. Replication using DNA from 76 African-Americans in the REason for Geographic and Racial Disparities in Cancer (REGARDS) study, as well as meta-analysis combining both cohorts was conducted. Results: Two differentially methylated CpG sites in the IGF2BP1 gene on chromosome 17 (cg06638433; β =0.01, p-value=3.10x10-7) and the ABCG1 gene on chromosome 21 (cg06500161; β: 0.018, p-value=2.60x10-8) were identified in models adjusted for age, sex, alcohol and smoking. Methylation of CpG sites on the TXNIP gene on chr 1 (p=2.83 x 10-9), and CPT1A gene on chr 11 (p=1.39 x 10-4) were also significantly associated with metabolic syndrome in unadjusted models. Results for the ABCG1 gene remained statistically significant in the replication set and meta-analysis. Conclusion: Metabolic syndrome was consistently associated with focal DNA hypermethylation in the ABCG1gene, a region of the chromosome that encodes proteins in the ATP-binding cassette transporter family, and is involved intra- and extra- cellular signaling. Alterations in the ABCG1 gene was observed in 40% of invasive breast cancer tumors in the TCGA, providing a potential epigenetic link between metabolic syndrome and breast cancer that deserves further study. Note: This abstract was not presented at the meeting. Citation Format: Tomi Akinyemiju. Epigenome-wide association study of metabolic syndrome in African-Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4243. doi:10.1158/1538-7445.AM2017-4243