Fig. 4

Transcriptomic changes in the stress system and DNA transmethylation reactions in the prefrontal cortex (BA10) of alcohol use disorder (AUD) subjects. mRNA levels of a enzymes of the DNA methylation pathway, i.e., DNA methyltransferases (DNMT) 1 (t_1,46= 3.16, p = 0.003), –3A (t_1,46= 2.28, p = 0.027), and –3B. These data remained significant after controlling for FDR (adjusted p-value = 0.003, 0.015, respectively). b Enzymes involved in DNA demethylation pathway, such as Ten-Eleven Translocase (TET) 1 (t_1,46= 2.17, p = 0.035), –2 (t_1,46= 2.25, p = 0.029), and –3 (t_1,46= 2.20, p = 0.034), as well as apolipoprotein B mRNA editing enzyme catalytic subunit 3C (APOBEC 3C) and growth arrest and DNA damage-inducible beta (GADD45B, t_1,46= 2.07, p = 0.044). These data remained significant after controlling for FDR (adjusted p-value = 0.061). c Glucocorticoid receptor cytosolic chaperones: FK506 binding protein 4 (FKBP4) and 51 (FKBP5, t_1,46= 2.49, p = 0.016), heat-shock protein 90 alpha family class A member 1 (HSP90AA1), heat-shock protein family A (Hsp70) member 4 (HSPA4, t_1,46= 2.11, p = 0.039), BCL2-associated athanogene 1 (BAG1, t_1,46= 2.16, p = 0.036). These data remained significant after controlling for FDR (adjusted p-value = 0.014). d Pearson’s correlation analysis of FKBP5 and NR3C1 mRNA levels. e Hypothalamic–pituitary–adrenal (HPA) axis neuroendocrine system: corticotropin-releasing factor (CRF, t_1,46= 2.52, p = 0.015), corticotropin-releasing factor receptor 1 (CRFR1, t_1,46= 2.19, p = 0.034), corticotropin-releasing factor receptor 2 (CRFR2, t_1,46= 2.19, p = 0.033), and proopiomelanocortin (POMC, t_1,46= 2.31, p = 0.026). These data remained significant after controlling for FDR (adjusted p-value = 0.037). f Pearson’s correlation analysis of CRF mRNA levels and ethanol daily use (g). g Mineralocorticoid receptor (NR3C2) mRNA expression levels (t_1,46 = 3.19, p = 0.002). Values are mean ± SEM of 24 samples per group. *p < 0.05, **p < 0.01, Student’s t-test vs. controls