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. 2022 Aug 11:13:972522.
doi: 10.3389/fpsyt.2022.972522. eCollection 2022.

The mediating role of transmembrane protein 132D methylation in predicting the occurrence of panic disorder in physical abuse

Qianmei Yu  1   2 , Chiyue Wang  2 , Huazheng Xu  2 , Yun Wu  1   2 , Huachen Ding  2 , Na Liu  1   2 , Ning Zhang  1   2 , Chun Wang  1   2
Affiliations

The mediating role of transmembrane protein 132D methylation in predicting the occurrence of panic disorder in physical abuse

Qianmei Yu et al. Front Psychiatry. .

Abstract

Objective: Genome Wide Association study (GWAS) has revealed that the transmembrane protein 132D (TMEM132D) is a gene of sensitive for panic disorder (PD). As the main type of childhood trauma experience, childhood abuse has become a public health issue attracting much attention at home and abroad, and has been proved to be a risk factor for the onset of PD. However, how it affects the occurrence and development of panic disorder has not yet been revealed. We examined the relationship between TMEM132D methylation, childhood abuse and symptoms based on this finding.

Materials and methods: Thirty-two patients with PD and 22 healthy controls (HCs) were recruited after age, gender, and the education level were matched. The DNA methylation levels of CpG sites across the genome were examined with genomic DNA samples (PD, N = 32, controls, N = 22) extracted from subjects' elbow venous blood. A mediation model was used to explore the relationship between the methylation degree of different CpG sites and childhood maltreatment and clinical symptoms.

Results: We found that the PD group had significantly lower methylation at CpG1, CpG2, CpG3, CpG4, CpG5, CpG6, CpG7, CpG8, CpG11, CpG14, and CpG18 than did the HCs (p < 0.05). The CpG2 (r = 0.5953, p = 0.0117) site in the priming region of TEME132D gene were positively associated with PDSS score. The CpG2 (r = 0.4889, p = 0.046) site in the priming region of TEME132D gene were positively associated with physical abuse. Furthermore, path analyses showed that the methylation of CpG2 of TMEM132D played a fully mediating role in the relationship between physical abuse and PD symptom severity (95.

Conclusion: Childhood abuse experiences, especially physical abuse, are significantly related to PD. The methylation of CpG2 of TMEM132D was shown to have a fully mediating effect between panic disorder and physical abuse. The interaction between TMEM132D methylation and physical abuse can predict panic disorder.

Keywords: TMEM132D; childhood trauma; emotional abuse; gene methylation; panic disorder.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Comparison of scores of childhood abuse scale between the panic disorder (PD) group (n = 32) and healthy controls (HCs) group (n = 22).*P < 0.05;**P < 0.01.
FIGURE 2
FIGURE 2
Comparison of methylation at CPG site of transmembrane protein132D (TMEM132D) gene in the panic disorder (PD) group and healthy control (HC) group, *p < 0.05;**p < 0.01.
FIGURE 3
FIGURE 3
(A) Correlation between CpG2 site methylation of transmembrane protein132D (TMEM132D) gene and PDSS score. The threshold was set at a significance level of p < 0.05. PDSS, Panic Disorder Severity Scale. (B) Correlation between CpG3 site methylation of TMEM132D gene and PDSS score. The threshold was set at a significance level of p < 0.05. PDSS, Panic Disorder Severity Scale. (C) Correlation between CpG2 site methylation of TMEM132D gene and physical abuse score. The threshold was set at a significance level of p < 0.05. (D) Correlation between CpG9 site methylation of TMEM132D gene and emotional abuse score. The threshold was set at a significance level of p < 0.05.
FIGURE 4
FIGURE 4
The mediating effect of transmembrane protein132D (TMEM132D) gene CPG site methylation in emotional abuse and panic symptoms.
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