Department of Psychiatry, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Sci Rep. 2021 Sep 16;11(1):18454. doi: 10.1038/s41598-021-98032-6.
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.
FKBP5 基因被认为在应激反应中的酒精使用障碍(AUD)中具有重要作用,并已被报道通过与儿童创伤相互作用来影响应激反应。本研究调查了 FKBP5 多态性 rs1360780 和儿童创伤对 AUD 男性患者特质韧性的影响。此外,还研究了 FKBP5 DNA 甲基化与韧性之间的等位基因特异性关联。共有 297 名 AUD 男性患者接受了酒精使用严重程度、儿童创伤、韧性和冲动性评估。对 FKBP5 rs1360780 进行基因分型,并分析 DNA 甲基化。使用线性回归分析测试 rs1360780 单核苷酸多态性(SNP)和临床变量对韧性的影响。使用偏相关分析测试 FKBP5 DNA 甲基化与韧性之间的可能关联。rs1360780 风险等位基因、低教育水平和高冲动性与韧性降低有关,而儿童创伤与 SNP rs1360780 基因型对韧性的主效应或交互效应均无显著意义。未发现 FKBP5 DNA 甲基化与韧性之间存在显著关联。本研究表明,FKBP5 中的 rs1360780 风险等位基因参与了 AUD 男性的特质韧性,这表明 FKBP5 的遗传易感性可能影响与 AUD 相关的韧性。