While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation—DNA methyltransferases (DNMTs)—has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder.

虽然 DNA 甲基化模式在焦虑症发病机制中的作用已被研究，但建立 DNA 甲基化的酶——DNA 甲基转移酶 (DNMT)——的作用仍有待研究。为了调查除了惊恐障碍的分类表型外，DNMT 基因型对维度焦虑特征的特异性影响，对 506 名惊恐障碍患者和 3112 名健康参与者进行了焦虑相关认知 [广场恐惧认知问卷 (ACQ)]、焦虑敏感性 [焦虑敏感性指数（ASI）]以及病理性担忧[宾夕法尼亚州立大学忧虑问卷（PSWQ）]，并对DNMT3A （rs11683424、rs1465764、rs1465825）和DNMT3B （rs2424932、rs4911259）基因中的五个单核苷酸多态性（SNP）进行基因分型，此前已发现这些与临床和性状相关的表型有关。与分类表型恐慌症没有关联。然而，在健康参与者中发现DNMT3A rs1465764 与 PSWQ 评分之间存在显着关联，其中次要等位基因具有保护作用。此外，还检测到健康参与者的问卷评分（PSWQ、ASI）与DNMT3B rs2424932 之间存在轻微显着关联，同样，次要等位基因也具有保护作用。目前的结果表明DNMT3A和DNMT3B基因变异在传达对焦虑症的恢复力方面可能发挥次要作用。由于观察到的关联表明两个 SNP 具有保护作用，尤其是对病理性担忧的保护作用，因此未来的研究建议探索广泛性焦虑症而不是恐慌症中的这些变异。