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

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.

Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption

“…Furthermore, animal studies have shown that HDAC4 inhibition increases sensitivity to cocaine, whereas overexpression of the gene has opposite effect, which further supports the importance of HDAC4 in conditioned place preference in addictive behaviour 57 . It is interesting to note that HDAC4 and HDAC5 belong to the same HDAC classification 55 , and HDAC5 gene has been associated previously with cocaine dependence in recent EWAS of cocaine and crack dependents 58 .…”

DNA methylation mediates the effect of cocaine use on HIV severity

“…Epigenetic mechanisms may play a role in cocaine's effect on the HIV severity because cocaine exposure has been showed to increase the expression of Methyl CpG binding protein 2 (MeCP2) expression [48] as well as DNMT3A and DNMT3B expressions [49] in the animal brains. In a well-matched, case-control human pilot study, cocaine use alters DNA methylation profile in blood [50]. It is plausible that cocaine use may lead to DNAm changes in immune response genes and gene expression changes in cytokine gene family, which further affects HIV progression.…”

A promising era for epigenetic research: revealing the molecular signature of neuropsychiatric disorders

“…The first studies were conducted in individuals with tobacco2 or alcohol substance disorder3 but, specifically regarding cocaine, evidence was limited to a single study that explored the state of peripheral DNA methylation in polysubstance abusers 4. A recent study published in this journal,5 however, has identified 186 differentially methylated positions between patients with cocaine use disorder (CUD) and healthy controls using bisulfite-converted DNA and genome-wide arrays. In this first epigenome-wide association study with CUD patients, the authors used a gene network approach among differentially methylated genes, revealing a pathway affected by CUD and implicated in gene transcription and chromatin regulation.…”