CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor

BACKGROUND: Genetic risks may predispose individuals to major mood disorders differently. This study investigated the gene polymorphisms of previously reported candidate genes for major depressive disorder (MDD) and bipolar disorder (BPD) in the Han Chinese population. METHODS: Twenty loci of 13 can...

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Autores principales: Zhang, Ting, Rao, Qingmin, Lin, Kangguang, He, Yongyin, Cai, Jintai, Yang, Mengxin, Xu, Ying, Hou, Le, Lin, Yulong, Liu, Haiying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9875448/
https://www.ncbi.nlm.nih.gov/pubmed/36698099
http://dx.doi.org/10.1186/s12888-022-04514-w
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author Zhang, Ting
Rao, Qingmin
Lin, Kangguang
He, Yongyin
Cai, Jintai
Yang, Mengxin
Xu, Ying
Hou, Le
Lin, Yulong
Liu, Haiying
author_facet Zhang, Ting
Rao, Qingmin
Lin, Kangguang
He, Yongyin
Cai, Jintai
Yang, Mengxin
Xu, Ying
Hou, Le
Lin, Yulong
Liu, Haiying
author_sort Zhang, Ting
collection PubMed
description BACKGROUND: Genetic risks may predispose individuals to major mood disorders differently. This study investigated the gene polymorphisms of previously reported candidate genes for major depressive disorder (MDD) and bipolar disorder (BPD) in the Han Chinese population. METHODS: Twenty loci of 13 candidate genes were detected by MALDI-TOF mass spectrometry in 439 patients with MDD, 600 patients with BPD, and 464 healthy controls. The distribution of genotypes in alleles, Hardy-Weinberg equilibrium, and genetic association were analyzed using the PLINK software. The linkage of disequilibrium and haplotype analyses were performed using the Haploview software. RESULTS: Out of the 20 loci analyzed, CYP2C19-rs4986893, ABCB1-rs1045642, and SCN2A-rs17183814 passed Bonferroni correction; their statistical powers were > 55%. The minor allele frequencies (MAF) of CYP2C19-rs4986893 in the MDD group (0.0547) and BPD group (0.0533) were higher than that of the control group (0.0259, P < 0.05), leading to the odds ratios (ORs) of MDD (2.178) and BPD (2.122), respectively. In contrast, the lower MAFs of ABCB1-rs1045642 were observed in both MDD (0.3599, OR = 0.726) and BPD (0.3700, OR = 0.758) groups than controls (0.4364, P < 0.05). The MDD group had a higher MAF of SCN2A-rs17183814 than controls (0.1743 vs. 0.1207, OR = 1.538, P < 0.05). Moreover, a G-A haplotype composed by CYP2C19-rs4986893 and -rs4244285 was associated with BPD (OR = 1.361, P < 0.01), and the A-G haplotype increased the risks to both MDD (OR = 2.306, P < 0.01) and BPD (OR = 2.332, P < 0.001). The CYP2C19 intermediate metabolizer and poor metabolizer (IM&PM) status was related to the raised risk of both MDD (OR = 1.547, P < 0.01) and BPD (OR = 1.808, P < 0.001). CONCLUSION: Our data indicate that the impaired CYP2C19 metabolism caused by the haplotypes integrated by CYP2C19 alleles might confer the risk to MDD and BPD, whereas the ABCB1-rs1045642 T allele serves as a protective factor.
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spelling pubmed-98754482023-01-26 CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor Zhang, Ting Rao, Qingmin Lin, Kangguang He, Yongyin Cai, Jintai Yang, Mengxin Xu, Ying Hou, Le Lin, Yulong Liu, Haiying BMC Psychiatry Research BACKGROUND: Genetic risks may predispose individuals to major mood disorders differently. This study investigated the gene polymorphisms of previously reported candidate genes for major depressive disorder (MDD) and bipolar disorder (BPD) in the Han Chinese population. METHODS: Twenty loci of 13 candidate genes were detected by MALDI-TOF mass spectrometry in 439 patients with MDD, 600 patients with BPD, and 464 healthy controls. The distribution of genotypes in alleles, Hardy-Weinberg equilibrium, and genetic association were analyzed using the PLINK software. The linkage of disequilibrium and haplotype analyses were performed using the Haploview software. RESULTS: Out of the 20 loci analyzed, CYP2C19-rs4986893, ABCB1-rs1045642, and SCN2A-rs17183814 passed Bonferroni correction; their statistical powers were > 55%. The minor allele frequencies (MAF) of CYP2C19-rs4986893 in the MDD group (0.0547) and BPD group (0.0533) were higher than that of the control group (0.0259, P < 0.05), leading to the odds ratios (ORs) of MDD (2.178) and BPD (2.122), respectively. In contrast, the lower MAFs of ABCB1-rs1045642 were observed in both MDD (0.3599, OR = 0.726) and BPD (0.3700, OR = 0.758) groups than controls (0.4364, P < 0.05). The MDD group had a higher MAF of SCN2A-rs17183814 than controls (0.1743 vs. 0.1207, OR = 1.538, P < 0.05). Moreover, a G-A haplotype composed by CYP2C19-rs4986893 and -rs4244285 was associated with BPD (OR = 1.361, P < 0.01), and the A-G haplotype increased the risks to both MDD (OR = 2.306, P < 0.01) and BPD (OR = 2.332, P < 0.001). The CYP2C19 intermediate metabolizer and poor metabolizer (IM&PM) status was related to the raised risk of both MDD (OR = 1.547, P < 0.01) and BPD (OR = 1.808, P < 0.001). CONCLUSION: Our data indicate that the impaired CYP2C19 metabolism caused by the haplotypes integrated by CYP2C19 alleles might confer the risk to MDD and BPD, whereas the ABCB1-rs1045642 T allele serves as a protective factor. BioMed Central 2023-01-25 /pmc/articles/PMC9875448/ /pubmed/36698099 http://dx.doi.org/10.1186/s12888-022-04514-w Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zhang, Ting
Rao, Qingmin
Lin, Kangguang
He, Yongyin
Cai, Jintai
Yang, Mengxin
Xu, Ying
Hou, Le
Lin, Yulong
Liu, Haiying
CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor
title CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor
title_full CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor
title_fullStr CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor
title_full_unstemmed CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor
title_short CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor
title_sort cyp2c19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the han chinese population whereas abcb1-rs1045642 acts as a protective factor
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9875448/
https://www.ncbi.nlm.nih.gov/pubmed/36698099
http://dx.doi.org/10.1186/s12888-022-04514-w
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