Analysis of genome-wide DNA methylation patterns in obesity

• Published in: ENDOCRINE JOURNAL Vol. 68; no. 12; pp. 1439 - 1453
• Main Authors: Wang, Chunhu, Wang, Meng, Ma, Jiguang
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Japan Endocrine Society 01.01.2021; Japan Science and Technology Agency
• Subjects: AMP; Calcium-binding protein; CpG islands; Cyclic AMP response element-binding protein; Deoxyribonucleic acid; DNA; DNA methylation; DNA methylation profiles; DNA microarrays; Epigenetics; Genomes; Homeobox; Inhibin; Obesity; Polymerase chain reaction; Reverse transcription; Signaling pathways; Troponin; Zinc finger proteins; Signaling pathways; Obesity; DNA methylation profiles
• ISSN: 0918-8959; 1348-4540
• DOI: 10.1507/endocrj.EJ20-0734

Obesity is a chronic and complex psychosomatic disease that is becoming increasingly prevalent worldwide. This study aimed to analyze whole methylation profiles to uncover the epigenetic mechanisms associated with obesity. DNA methylation profiles in blood samples from patients with obesity and normal controls were studied using the Illumina 850 K methylation microarray. The diagnostic value of the differentially methylated genes was determined using receiver operating characteristic (ROC) analysis. The expression of selected candidate genes was verified using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and pyrosequencing. A total of 9,371 significantly differentially methylated sites (7,974 hypermethylated sites and 1,397 hypomethylated sites) were identified in 4,571 genes. A difference in the distribution of differentially methylated sites (hypermethylated and hypomethylated) in both gene structures and CpG islands was observed. A total of 114 key differentially methylated sites were identified in the CpG islands. ROC results indicated that Inhibin Subunit Beta B (INHBB), Homeobox A9 (HOXA9), Troponin T3 (TNNT3), Cyclic adenosine monophosphate (cAMP)-responsive element binding protein (CREB)-regulated transcription coactivator 1 (CRTC1) and Zinc finger and BTB domain-containing 7 B (ZBTB7B) could discriminate patients with obesity from normal controls. RT-qPCR results of CRTC1 and ZBTB7B were consistent with our methylation profile results. The pyrosequencing results showed that the methylation levels of CRTC1 CpG sites (CpG1 and CpG2-cg11660071) and INHBB CpG sites (CpG2) were significantly changed in patients with obesity compared with normal controls, which was consistent with our DNA methylation profile results. Our study provides new insights into the pathological mechanism of obesity.