Genome-Wide DNA Methylation Profiles of Phlegm-Dampness Constitution

Cell Physiol Biochem. 2018;45(5):1999-2008. doi: 10.1159/000487976. Epub 2018 Mar 2.

Abstract

Background/aims: Metabolic diseases are leading health concerns in today's global society. In traditional Chinese medicine (TCM), one body type studied is the phlegm-dampness constitution (PC), which predisposes individuals to complex metabolic disorders. Genomic studies have revealed the potential metabolic disorders and the molecular features of PC. The role of epigenetics in the regulation of PC, however, is unknown.

Methods: We analyzed a genome-wide DNA methylation in 12 volunteers using Illumina Infinium Human Methylation450 BeadChip on peripheral blood mononuclear cells (PBMCs). Eight volunteers had PC and 4 had balanced constitutions.

Results: Methylation data indicated a genome-scale hyper-methylation pattern in PC. We located 288 differentially methylated probes (DMPs). A total of 256 genes were mapped, and some of these were metabolic-related. SQSTM1, DLGAP2 and DAB1 indicated diabetes mellitus; HOXC4 and SMPD3, obesity; and GRWD1 and ATP10A, insulin resistance. According to Ingenuity Pathway Analysis (IPA), differentially methylated genes were abundant in multiple metabolic pathways.

Conclusion: Our results suggest the potential risk for metabolic disorders in individuals with PC. We also explain the clinical characteristics of PC with DNA methylation features.

Keywords: Bioinformatics; Chinese medicine; Dna methylation; Peripheral blood mononuclear cells; Phlegm-dampness constitution.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adult
  • Carrier Proteins / genetics
  • CpG Islands
  • DNA Methylation*
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / pathology
  • Epigenesis, Genetic
  • Female
  • Homeodomain Proteins / genetics
  • Humans
  • Insulin Resistance
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Membrane Transport Proteins / genetics
  • Metabolic Diseases / genetics*
  • Metabolic Diseases / pathology
  • Middle Aged
  • Nerve Tissue Proteins / genetics
  • Obesity / pathology
  • Oligonucleotide Array Sequence Analysis
  • Sphingomyelin Phosphodiesterase / genetics

Substances

  • Carrier Proteins
  • DLGAP2 protein, human
  • GRWD1 protein, human
  • HOXC4 protein, human
  • Homeodomain Proteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SMPD3 protein, human
  • Sphingomyelin Phosphodiesterase
  • Adenosine Triphosphatases
  • ATP10A protein, human