An investigation of genetic variability of DNA methyltransferasesDNMT3Aand3Bdoes not provide evidence for a major role in the pathogenesis of panic disorder and dimensional anxiety phenotypes

Berking, Ann-Cathrine; Thiel, Christiane; Schiele, Miriam A.; Baumann, Christian; Kalisch, Raffael; Notzen, Swantje; Zwanzger, Peter; Pane-Farre, Christiane A.; Hamm, Alfons; Alpers, Georg W.; Fydrich, Thomas; Fehm, Lydia; Gerlach, Alexander L.; Straube, Benjamin; Kircher, Tilo; Rief, Winfried; Plag, Jens; Stroehle, Andreas; Lang, Thomas; Wittchen, Hans-Ulrich; Arolt, Volker; Romanos, Marcel; Pauli, Paul; Reif, Andreas; Deckert, Jürgen; Domschke, Katharina and Weber, Heike (2020): An investigation of genetic variability of DNA methyltransferasesDNMT3Aand3Bdoes not provide evidence for a major role in the pathogenesis of panic disorder and dimensional anxiety phenotypes. In: Journal of Neural Transmission, Vol. 127, No. 11: pp. 1527-1537

Abstract

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 theDNMT3A(rs11683424, rs1465764, rs1465825) andDNMT3B(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 betweenDNMT3Ars1465764 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 andDNMT3Brs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role ofDNMT3AandDNMT3Bgene 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.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 0300-9564
• Language: English