Genome-wide DNA methylation profile in the peripheral blood of cocaine and crack dependents

Braz J Psychiatry. 2019 Nov-Dec;41(6):485-493. doi: 10.1590/1516-4446-2018-0092.

Abstract

Objective: Cocaine use disorders (CUDs) represent a major public health problem in many countries. To better understand the interaction between the environmental modulations and phenotype, the aim of the present study was to investigate the DNA methylation pattern of CUD patients, who had concomitant cocaine and crack dependence, and healthy controls.

Methods: We studied DNA methylation profiles in the peripheral blood of 23 CUD patients and 24 healthy control subjects using the Illumina Infinium HumanMethylation450 BeadChip arrays.

Results: Comparison between CUD patients and controls revealed 186 differentially methylated positions (DMPs; adjusted p-value [adjP] < 10-5) related to 152 genes, with a subset of CpGs confirmed by pyrosequencing. DNA methylation patterns discriminated CUD patients and control groups. A gene network approach showed that the EHMT1, EHMT2, MAPK1, MAPK3, MAP2K1, and HDAC5 genes, which are involved in transcription and chromatin regulation cellular signaling pathways, were also associated with cocaine dependence.

Conclusion: The investigation of DNA methylation patterns may contribute to a better understanding of the biological mechanisms involved in CUD.

MeSH terms

  • Adult
  • Case-Control Studies
  • Cocaine-Related Disorders / blood*
  • Cocaine-Related Disorders / genetics*
  • Crack Cocaine*
  • DNA Methylation*
  • Gene Regulatory Networks
  • Genome-Wide Association Study / methods*
  • High-Throughput Nucleotide Sequencing
  • Histocompatibility Antigens / genetics
  • Histone Deacetylases / genetics
  • Histone-Lysine N-Methyltransferase / genetics
  • Humans
  • Linear Models
  • MAP Kinase Kinase 1 / genetics
  • Male
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Statistics, Nonparametric
  • Young Adult

Substances

  • Crack Cocaine
  • Histocompatibility Antigens
  • EHMT1 protein, human
  • EHMT2 protein, human
  • Histone-Lysine N-Methyltransferase
  • MAPK1 protein, human
  • MAPK3 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • MAP Kinase Kinase 1
  • HDAC5 protein, human
  • Histone Deacetylases