Next-generation sequencing methylation profiling of subjects with obesity identifies novel gene changes

• Published in: Clinical epigenetics 2016-07, Vol.8 (1), p.77, Article 77
• Main Authors: Day, Samantha E, Coletta, Richard L, Kim, Joon Young, Campbell, Latoya E, Benjamin, Tonya R, Roust, Lori R, De Filippis, Elena A, Dinu, Valentin, Shaibi, Gabriel Q, Mandarino, Lawrence J, Coletta, Dawn K
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adult; Care and treatment; Development and progression; DNA Methylation; Epigenesis, Genetic; Female; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation; Genetic aspects; Health aspects; High-Throughput Nucleotide Sequencing - methods; Humans; Male; Obesity; Obesity - genetics; Oligonucleotide Array Sequence Analysis - methods; Promoter Regions, Genetic; Sequence Analysis, DNA - methods; Sequence Analysis, RNA - methods; Transcription factors
• ISSN: 1868-7075; 1868-7083; 1868-7083; 1868-7075
• DOI: 10.1186/s13148-016-0246-x

Obesity is a metabolic disease caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are incompletely understood. The aim of our study was to investigate the role of skeletal muscle DNA methylation in combination with transcriptomic changes in obesity. Muscle biopsies were obtained basally from lean (n = 12; BMI = 23.4 ± 0.7 kg/m(2)) and obese (n = 10; BMI = 32.9 ± 0.7 kg/m(2)) participants in combination with euglycemic-hyperinsulinemic clamps to assess insulin sensitivity. We performed reduced representation bisulfite sequencing (RRBS) next-generation methylation and microarray analyses on DNA and RNA isolated from vastus lateralis muscle biopsies. There were 13,130 differentially methylated cytosines (DMC; uncorrected P