ArticleTranslational psychiatry2018
Polymorphism in Tmem132d regulates expression and anxiety-related behavior through binding of RNA polymerase II complex.
Article in Translational psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 110 citations in OpenAlex.
- Beyond fear circuits: multiscale neurobiological architecture of panic disorder.Molecular psychiatry · 2026Pooled it
- Unveiling the enigma of anxiety disorders and depression: from pathogenesis to treatment.Science China. Life sciences · 2026Review
- Tinnitus and tinnitus disorder: Genetic, neurobiological, and clinical differentiation.iScience · 2026Review
- Mourning for Silence: Bereavement and Tinnitus-A Perspective.Journal of clinical medicine · 2025Article
- PRKCB methylation: a potential biomarker of MDD with childhood chronic stress, a cross-sectional study in drug-naive, first-episode adolescent MDD.Epigenetics · 2024Observational
- Immunoglobulin genes expressed in lymphoblastoid cell lines discern and predict lithium response in bipolar disorder patients.Molecular psychiatry · 2023Article
- Genome-wide association and replication studies for handedness in a Korean community-based cohort.Brain and behavior · 2023Article
- TMEM132D and VIPR2 Polymorphisms as Genetic Risk Loci for Retinal Detachment: A Genome-Wide Association Study and Polygenic Risk Score Analysis.Investigative ophthalmology & visual science · 2023Article
- Differential expression of the Tmem132 family genes in the developing mouse nervous system.Gene expression patterns : GEP · 2022Article
- Effects of stressful life-events on DNA methylation in panic disorder and major depressive disorder.Clinical epigenetics · 2022Article
- The mediating role of transmembrane protein 132D methylation in predicting the occurrence of panic disorder in physical abuse.Frontiers in psychiatry · 2022Article
- Roles, molecular mechanisms, and signaling pathways of TMEMs in neurological diseases.American journal of translational research · 2021Review
- Epigenetic Mechanisms Within the Cingulate Cortex Regulate Innate Anxiety-Like Behavior.The international journal of neuropsychopharmacology · 2019Article
- A Latent Gaussian Copula Model for Mixed Data Analysis in Brain Imaging Genetics.IEEE/ACM transactions on computational biology and bioinformaticsArticle
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TMEM132D is a candidate gene, where risk genotypes have been associated with anxiety severity along with higher mRNA expression in the frontal cortex of panic disorder patients. Concurrently, in a high (HAB) and low (LAB) trait anxiety mouse model, Tmem132d was found to show increased expression in the anterior cingulate cortex (aCC) of HAB as compared to LAB mice. To understand the molecular underpinnings underlying the differential expression, we sequenced the gene and found two single-nucleotide polymorphisms (SNPs) in the promoter differing between both lines which could explain the observed mRNA expression profiles using gene reporter assays. In addition, there was no difference in basal DNA methylation in the CpG Island that encompasses the HAB vs. LAB Tmem132d promoter region. Furthermore, we found significantly higher binding of RNA polymerase II (POLR2A) to the proximal HAB-specific SNP (rs233264624) than the corresponding LAB locus in an oligonucleotide pull-down assay, suggesting increased transcription. Virus mediated overexpression of Tmem132d in the aCC of C57BL/6 J mice could confirm its role in mediating an anxiogenic phenotype. To model gene-environmental interactions, HAB mice exposed to enriched environment (HAB-EE) responded with decreased anxiety levels but, had enhanced Tmem132d mRNA expression as compared to standard-housed HAB (HAB-SH) mice. While LAB mice subjected to unpredictable chronic mild stress (LAB-UCMS) exhibited higher anxiety levels and had lower mRNA expression compared to standard-housed LAB (LAB-SH) mice. Chromatin immunoprecipitation revealed significantly higher binding of POLR2A to rs233264624 in HAB-EE, while LAB-UCMS had lower POLR2A binding at this locus, thus explaining the enhanced or attenuated expression of Tmem132d compared to their respective SH controls. To further investigate gene-environment interactions, DNA methylation was assessed using Illumina 450 K BeadChip in 74 panic disorder patients. Significant methylation differences were observed in two CpGs (cg26322591 and cg03283235) located in TMEM132D depending on the number of positive life events supporting the results of an influence of positive environmental cues on regulation of Tmem132d expression in mice.
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