1Department of Epidemiology, University of Kentucky, Lexington, KY USA.
2Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL USA.
Clin Epigenetics. 2018 Apr 10;10:49. doi: 10.1186/s13148-018-0483-2. eCollection 2018.
The high prevalence 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 may provide additional information regarding etiology beyond current evidence from genome-wide association studies.
Data on metabolic syndrome and DNA methylation was assessed on 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.
Two differentially methylated CpG sites in the gene on chromosome 17 (cg06638433; value = 3.10 × 10) and the gene on chromosome 21 (cg06500161; value = 2.60 × 10) were identified. Results for the gene remained statistically significant in the replication dataset and meta-analysis.
Metabolic syndrome was consistently associated with increased methylation in the 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.
美国成年人肥胖的高患病率导致相关代谢紊乱（如糖尿病、血脂异常和高血压）显著增加。这些疾病共同构成了代谢综合征，这是一种在非裔美国人中高度流行的临床定义疾病。鉴定与代谢综合征相关的表观遗传改变可能会提供除全基因组关联研究之外的更多关于病因的信息。
在高血压遗传流行病学网络（HyperGEN）研究中，对 614 名非裔美国人的代谢综合征和 DNA 甲基化数据进行了评估。代谢综合征的定义采用联合协调标准，使用 Illumina HumanMethylation450K Bead Chip 试剂盒检测从白细胞提取的 DNA 的 CpG 甲基化。线性混合效应回归模型用于检验超过 450,000 个 CpG 位点的 CpG 甲基化与代谢综合征之间的关联，调整了研究协变量。使用来自另外 69 名非裔美国人的 DNA 进行了复制，以及结合两个队列的荟萃分析。
在染色体 17 上的 基因（cg06638433； 值=3.10×10）和染色体 21 上的 基因（cg06500161； 值=2.60×10）中发现了两个差异甲基化的 CpG 位点。在复制数据集和荟萃分析中， 基因的结果仍然具有统计学意义。
在发现和复制数据集，代谢综合征与 基因的甲基化增加一致相关，该基因编码 ABC 转运蛋白家族的蛋白质，参与细胞内和细胞外信号转导和脂质转运。
