Interaction between CRHR1 and BDNF genes increases the risk of recurrent major depressive disorder in Chinese population
Open accessAbstract
BACKGROUND: An important etiological hypothesis about depression is stress has neurotoxic effects that damage the hippocampal cells. Corticotropin-releasing hormone (CRH) regulates brain-derived neurotrophic factor (BDNF) expression through influencing cAMP and Ca2+ signaling pathways during the course. The aim of this study is to examine the single and combined effects of CRH receptor 1 (CRHR1) and BDNF genes in recurrent major depressive disorder (MDD). METHODOLOGY/PRINCIPAL FINDING: The sample consists of 181 patients with recurrent MDD and 186 healthy controls. Whether genetic variations interaction between CRHR1 and BDNF genes might be associated with increased susceptibility to recurrent MDD was studied by using a gene-based association analysis of single-nucleotide polymorphisms (SNPs). CRHR1 gene (rs1876828, rs242939 and rs242941) and BDNF gene (rs6265) were identified in the samples of patients diagnosed with recurrent MDD and matched controls. Allelic association between CRHR1 rs242939 and recurrent MDD was found in our sample (allelic: p = 0.018, genotypic: p = 0.022) with an Odds Ratio 0.454 (95% CI 0.266-0.775). A global test of these four haplotypes showed a significant difference between recurrent MDD group and control group (chi-2 = 13.117, df = 3, P = 0.016. Furthermore, BDNF and CRHR1 interactions were found in the significant 2-locus, gene-gene interaction models (p = 0.05) using a generalized multifactor dimensionality reduction (GMDR) method. CONCLUSION: Our results suggest that an interaction between CRHR1 and BDNF genes constitutes susceptibility to recurrent MDD.
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Mutations in BDNF and serotonin receptor genes are associated with recurrent MDD.
“Mutations in the brain-derived neurotropic factor (BDNF) [29, 30] and serotonin receptor genes [31] were shown to be associated with recurrent MDD.”
From Predictors of recurrence of major depressive disorder (2020) · cites this paper as [30]
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Predictors of recurrence of major depressive disorder
Lye, M.-S., Tey, Y.-Y., Tor, Y.-S., Shahabudin, A. F., Ibrahim, N., Ling, K.-H., Stanslas, J., Loh, S.-P., Rosli, R., Lokman, K. A., et al. (2020) · PLOS ONE · doi:10.1371/journal.pone.0230363 · Cited by 43 · see citing works
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- Authors
- Xiao, Z., Liu, W., Gao, K., Wan, Q., Yang, C., Wang, H., Wang, X., Wang, G., & Liu, Z.
- Affiliations
- Wuhan University (CN)
- Corresponding author
- Liu, Zhongchun
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-12-14
- Volume
- 6
- Issue
- 12
- Pages
- e28733
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3237493
- OpenAlex
- W2014228664
- Cited by
- 37
- References
- 36
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 5 · 2015: 3 · 2014: 5 · 2013: 2 · 2012: 3
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (30971040)
- Wuhan University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- recurrent major depressive disorder, CRHR1, brain-derived neurotrophic factor, gene-gene interaction, genetic susceptibility, single nucleotide polymorphisms, BDNF Val66Met polymorphism, haplotypes, Chinese population
- MeSH terms
- CRF Receptor, Type 1, Adult, Alleles, China, Major Depressive Disorder, Epistasis, Genetic, Female, Gene Frequency, Haplotypes, Humans, Male, Models, Genetic, Recurrence, Risk Factors, Case-Control Studies, Receptors, Corticotropin-Releasing Hormone, Brain-Derived Neurotrophic Factor, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Asian People, Multifactor Dimensionality Reduction
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