Analysis of the association of MIR124-1 and its target gene RGS4 polymorphisms with major depressive disorder and antidepressant response

Duan Zeng,1,* Shen He,1,* Shunying Yu,1 Guanjun Li,1 Changlin Ma,2 Yi Wen,2 Yifeng Shen,1 Yimin Yu,1 Huafang Li1,3 1Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Jiading District M...

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Autores principales:	Zeng D, He S, Yu S, Li G, Ma C, Wen Y, Shen Y, Yu Y, Li H
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Polymorphisms MIR124-1 Regulator of G protein signaling 4 Depression Antidepressant Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/1598414897794c9291fe436da16e2b38
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spelling	oai:doaj.org-article:1598414897794c9291fe436da16e2b382021-12-02T03:54:03ZAnalysis of the association of MIR124-1 and its target gene RGS4 polymorphisms with major depressive disorder and antidepressant response1178-2021https://doaj.org/article/1598414897794c9291fe436da16e2b382018-03-01T00:00:00Zhttps://www.dovepress.com/analysis-of-the-association-of-mir124-1-and-its-target-gene-rgs4-polym-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Duan Zeng,1,* Shen He,1,* Shunying Yu,1 Guanjun Li,1 Changlin Ma,2 Yi Wen,2 Yifeng Shen,1 Yimin Yu,1 Huafang Li1,3 1Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Jiading District Mental Health Center, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Increasing evidence has indicated that dysfunction of miR-124 and target gene regulator of G protein signaling 4 (RGS4) may be involved in the etiology and treatment of major depressive disorder (MDD). However, the molecular mechanisms are not fully understood. This study aimed to investigate whether common genetic variations in these two genes are associated with MDD and therapeutic response to antidepressants in the Chinese population. Methods: Three polymorphisms including rs531564 (a functional single-nucleotide polymorphism [SNP] in MIR124-1), rs10759 (a microRNA-binding site SNP in RGS4), and rs951436 (a promoter SNP in RGS4) were genotyped in 225 Chinese MDD patients and 436 controls. Among the MDD patients, 147 accepted antidepressant treatment for 8 weeks with therapeutic evaluation at baseline, week 2, week 4, week 6, and week 8 using the 17-item Hamilton Rating Scale for Depression. Multifactor dimensionality reduction (MDR) was used to identify gene–gene interactions. Results: No significant association with MDD was discovered in single-SNP analyses. However, by MDR analysis, the three-locus model of gene–gene interaction was the best for predicting MDD risk. In pharmacogenetic study, a significant association was found in genotypic frequencies of rs951436 between the remitter and non-remitter groups (p=0.026, correction p=0.078). For further analysis, the rs951436 heterozygote carriers had threefold probabilities of achieving clinical complete remission (odds ratio =3.00, 95% confidence interval =1.33–6.76, p=0.007, correction p=0.021) as compared with rs951436 homozygotes (AA+CC) after 8 weeks of treatment. Conclusion: An interaction effect of MIR124-1 and RGS4 polymorphisms may play a more important role than individual factors for MDD development. Moreover, RGS4 gene polymorphisms may be associated with antidepressant response among the Han population. Keywords: polymorphisms, MIR124-1, regulator of G protein signaling 4, depression, antidepressant, gene–gene interactionZeng DHe SYu SLi GMa CWen YShen YYu YLi HDove Medical PressarticlePolymorphismsMIR124-1Regulator of G protein signaling 4DepressionAntidepressantNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 14, Pp 715-723 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Polymorphisms MIR124-1 Regulator of G protein signaling 4 Depression Antidepressant Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Polymorphisms MIR124-1 Regulator of G protein signaling 4 Depression Antidepressant Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Zeng D He S Yu S Li G Ma C Wen Y Shen Y Yu Y Li H Analysis of the association of MIR124-1 and its target gene RGS4 polymorphisms with major depressive disorder and antidepressant response
description	Duan Zeng,1,* Shen He,1,* Shunying Yu,1 Guanjun Li,1 Changlin Ma,2 Yi Wen,2 Yifeng Shen,1 Yimin Yu,1 Huafang Li1,3 1Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Jiading District Mental Health Center, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Increasing evidence has indicated that dysfunction of miR-124 and target gene regulator of G protein signaling 4 (RGS4) may be involved in the etiology and treatment of major depressive disorder (MDD). However, the molecular mechanisms are not fully understood. This study aimed to investigate whether common genetic variations in these two genes are associated with MDD and therapeutic response to antidepressants in the Chinese population. Methods: Three polymorphisms including rs531564 (a functional single-nucleotide polymorphism [SNP] in MIR124-1), rs10759 (a microRNA-binding site SNP in RGS4), and rs951436 (a promoter SNP in RGS4) were genotyped in 225 Chinese MDD patients and 436 controls. Among the MDD patients, 147 accepted antidepressant treatment for 8 weeks with therapeutic evaluation at baseline, week 2, week 4, week 6, and week 8 using the 17-item Hamilton Rating Scale for Depression. Multifactor dimensionality reduction (MDR) was used to identify gene–gene interactions. Results: No significant association with MDD was discovered in single-SNP analyses. However, by MDR analysis, the three-locus model of gene–gene interaction was the best for predicting MDD risk. In pharmacogenetic study, a significant association was found in genotypic frequencies of rs951436 between the remitter and non-remitter groups (p=0.026, correction p=0.078). For further analysis, the rs951436 heterozygote carriers had threefold probabilities of achieving clinical complete remission (odds ratio =3.00, 95% confidence interval =1.33–6.76, p=0.007, correction p=0.021) as compared with rs951436 homozygotes (AA+CC) after 8 weeks of treatment. Conclusion: An interaction effect of MIR124-1 and RGS4 polymorphisms may play a more important role than individual factors for MDD development. Moreover, RGS4 gene polymorphisms may be associated with antidepressant response among the Han population. Keywords: polymorphisms, MIR124-1, regulator of G protein signaling 4, depression, antidepressant, gene–gene interaction
format	article
author	Zeng D He S Yu S Li G Ma C Wen Y Shen Y Yu Y Li H
author_facet	Zeng D He S Yu S Li G Ma C Wen Y Shen Y Yu Y Li H
author_sort	Zeng D
title	Analysis of the association of MIR124-1 and its target gene RGS4 polymorphisms with major depressive disorder and antidepressant response
title_short	Analysis of the association of MIR124-1 and its target gene RGS4 polymorphisms with major depressive disorder and antidepressant response
title_full	Analysis of the association of MIR124-1 and its target gene RGS4 polymorphisms with major depressive disorder and antidepressant response
title_fullStr	Analysis of the association of MIR124-1 and its target gene RGS4 polymorphisms with major depressive disorder and antidepressant response
title_full_unstemmed	Analysis of the association of MIR124-1 and its target gene RGS4 polymorphisms with major depressive disorder and antidepressant response
title_sort	analysis of the association of mir124-1 and its target gene rgs4 polymorphisms with major depressive disorder and antidepressant response
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/1598414897794c9291fe436da16e2b38
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Analysis of the association of MIR124-1 and its target gene RGS4 polymorphisms with major depressive disorder and antidepressant response

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