Genetic association of FKBP5 with trait resilience in Korean male patients with alcohol use disorder

Jee In Kang,Hae Won Kim,Chun Il Park,Syung Shick Hwang,Se Joo Kim

doi:10.1038/s41598-021-98032-6

Jee In Kang, Hae Won Kim + Show 3 more

Open Access

https://doi.org/10.1038/s41598-021-98032-6

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Abstract

The FKBP5 gene is known to have an important role in alcohol use disorder (AUD) in response to stress and has been reported to affect stress responses by interacting with childhood trauma. This study investigated the effects of the FKBP5 polymorphism rs1360780 and childhood trauma on trait resilience in male patients with AUD. In addition, allele-specific associations between FKBP5 DNA methylation and resilience were examined. In total, 297 men with AUD were assessed for alcohol use severity, childhood trauma, resilience, and impulsivity. Genotyping for FKBP5 rs1360780 and DNA methylation were analyzed. The effects of the rs1360780 single nucleotide polymorphism (SNP) and clinical variables on resilience were tested using linear regression analysis. Possible associations between FKBP5 DNA methylation and resilience were tested with partial correlation analysis. The rs1360780 risk allele, a low education level, and high impulsivity were associated with diminished resilience, whereas no significant main or interaction effect of childhood trauma with the SNP rs1360780 genotype on resilience was shown. No significant association between FKBP5 DNA methylation and resilience was found. The present study demonstrated the involvement of the rs1360780 risk allele in trait resilience in men with AUD, suggesting that the genetic vulnerability of FKBP5 may influence resilience related to AUD.

Highlights

The FKBP5 gene is known to have an important role in alcohol use disorder (AUD) in response to stress and has been reported to affect stress responses by interacting with childhood trauma
The demographic and clinical characteristics of the participants with AUD are presented in Table 1 according to genotype groups of FKBP5 rs1360780
The present study showed that the FKBP5 rs1360780 risk allele, a low education level, and high impulsivity were associated with diminished resilience in Korean male patients with AUD, whereas no significant main or interaction effect of childhood trauma with the FKBP5 gene on resilience was shown

Summary

Introduction

The FKBP5 gene is known to have an important role in alcohol use disorder (AUD) in response to stress and has been reported to affect stress responses by interacting with childhood trauma. FKBP51 is a major regulatory protein of the HPA axis and is known to modulate glucocorticoid receptor (GR) sensitivity by binding to GRs in the cytosol and reducing GR nuclear translocation in response to s tressors[9,10,11] It is an important molecular target of human stress responses and psychiatric disorders, including AUD12,13. Rs1360780 in FKBP5, the most widely studied genetic polymorphism in stressrelated psychiatric disorders, was reported to have an interaction effect with childhood trauma on predicting heavy alcohol consumption (a risk factor for AUD) in nonclinical college s tudents[16]. Years Education, years Duration of AUD, years AUDIT BIS RQT Childhood trauma (n) Higher Lower FKBP5 methylation (%) CpG1 CpG2

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