Sex-specific effects of methylenetetrahydrofolate reductase polymorphisms on schizophrenia with methylation changes
Background: Methylenetetrahydrofolate reductase (MTHFR) is the critical enzyme in biotransformation. The polymorphism of MTHFR is a risk factor for schizophrenia. However, whether the MTHFR polymorphism is associated with schizophrenia disease phenotypes and what is the underlying mechanism of MTHFR...
Ausführliche Beschreibung
Autor*in: |
Lin Wan [verfasserIn] Guofu Zhang [verfasserIn] Min Liu [verfasserIn] Chuanyue Wang [verfasserIn] Yuhong Li [verfasserIn] Rena Li [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2019 |
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Übergeordnetes Werk: |
In: Comprehensive Psychiatry - Elsevier, 2019, 94(2019), Seite - |
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Übergeordnetes Werk: |
volume:94 ; year:2019 ; pages:- |
Links: |
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DOI / URN: |
10.1016/j.comppsych.2019.152121 |
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Katalog-ID: |
DOAJ032173539 |
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520 | |a Background: Methylenetetrahydrofolate reductase (MTHFR) is the critical enzyme in biotransformation. The polymorphism of MTHFR is a risk factor for schizophrenia. However, whether the MTHFR polymorphism is associated with schizophrenia disease phenotypes and what is the underlying mechanism of MTHFR polymorphism in schizophrenia is under-investigated. In this study, we aim to verify the correlation between MTHFR polymorphisms and clinical features of schizophrenia, while exploring the differential genomic methylation and disease related genes as the potential targets for schizophrenia. Method: 242 patients of schizophrenia and 234 matched healthy controls were enrolled in this study. Polymorphisms of MTHFR from three sites (C677T, A1298C, G1793A) were examined by Taqman fluorescence probe method in leukocytes from all subjects. The positive and negative syndrome scale (PANSS), trail making test (TMT) and Clinical Global Impression (CGI) were checked on patients. Genomic methylation was tested and analyzed in fields of differential methylation positions (DMPs) and enrichment of genes that are potentially related to schizophrenia. Results: Schizophrenic patients showed higher frequency of MTHFR polymorphisms at both single and multiple sites than healthy controls. Our data also showed that MTHFR C677T and multiple-site polymorphisms were positively correlated with PANSS positive rating, not negative score in male schizophrenia patients. Furthermore, while a significant reduction of global DNA methylation level was observed in schizophrenic patients, we also identified several genes which differentiated between schizophrenia and healthy controls at methylation levels. Conclusions: This is a pilot study revealing that MTHFR polymorphisms at both single and multiple sites are related to the risk of schizophrenia and positive symptom of the disease. The risk of MTHFR polymorphism in schizophrenia and the clinical symptoms was only significant in male patients. While the sex-specific risk of MTHFR in schizophrenia is new and the reasons remain unanswered. Our methylation analysis suggested that there was significant hypomethylation of genomic DNA in schizophrenia patients with no sex difference. The correlation between MTHFR polymorphism and schizophrenia may attribute to the change of DNA methylation level, and some certain genes could be potential research objects for MTHFR effects on schizophrenia. Keywords: MTHFR, Schizophrenia, Polymorphism, Symptom, Methylation | ||
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700 | 0 | |a Rena Li |e verfasserin |4 aut | |
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10.1016/j.comppsych.2019.152121 doi (DE-627)DOAJ032173539 (DE-599)DOAJ857c0a71fdc3462aa355be763bb8cac3 DE-627 ger DE-627 rakwb eng RC435-571 Lin Wan verfasserin aut Sex-specific effects of methylenetetrahydrofolate reductase polymorphisms on schizophrenia with methylation changes 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Methylenetetrahydrofolate reductase (MTHFR) is the critical enzyme in biotransformation. The polymorphism of MTHFR is a risk factor for schizophrenia. However, whether the MTHFR polymorphism is associated with schizophrenia disease phenotypes and what is the underlying mechanism of MTHFR polymorphism in schizophrenia is under-investigated. In this study, we aim to verify the correlation between MTHFR polymorphisms and clinical features of schizophrenia, while exploring the differential genomic methylation and disease related genes as the potential targets for schizophrenia. Method: 242 patients of schizophrenia and 234 matched healthy controls were enrolled in this study. Polymorphisms of MTHFR from three sites (C677T, A1298C, G1793A) were examined by Taqman fluorescence probe method in leukocytes from all subjects. The positive and negative syndrome scale (PANSS), trail making test (TMT) and Clinical Global Impression (CGI) were checked on patients. Genomic methylation was tested and analyzed in fields of differential methylation positions (DMPs) and enrichment of genes that are potentially related to schizophrenia. Results: Schizophrenic patients showed higher frequency of MTHFR polymorphisms at both single and multiple sites than healthy controls. Our data also showed that MTHFR C677T and multiple-site polymorphisms were positively correlated with PANSS positive rating, not negative score in male schizophrenia patients. Furthermore, while a significant reduction of global DNA methylation level was observed in schizophrenic patients, we also identified several genes which differentiated between schizophrenia and healthy controls at methylation levels. Conclusions: This is a pilot study revealing that MTHFR polymorphisms at both single and multiple sites are related to the risk of schizophrenia and positive symptom of the disease. The risk of MTHFR polymorphism in schizophrenia and the clinical symptoms was only significant in male patients. While the sex-specific risk of MTHFR in schizophrenia is new and the reasons remain unanswered. Our methylation analysis suggested that there was significant hypomethylation of genomic DNA in schizophrenia patients with no sex difference. The correlation between MTHFR polymorphism and schizophrenia may attribute to the change of DNA methylation level, and some certain genes could be potential research objects for MTHFR effects on schizophrenia. Keywords: MTHFR, Schizophrenia, Polymorphism, Symptom, Methylation Psychiatry Guofu Zhang verfasserin aut Min Liu verfasserin aut Chuanyue Wang verfasserin aut Yuhong Li verfasserin aut Rena Li verfasserin aut In Comprehensive Psychiatry Elsevier, 2019 94(2019), Seite - (DE-627)330080377 (DE-600)2049049-5 15328384 nnns volume:94 year:2019 pages:- https://doi.org/10.1016/j.comppsych.2019.152121 kostenfrei https://doaj.org/article/857c0a71fdc3462aa355be763bb8cac3 kostenfrei http://www.sciencedirect.com/science/article/pii/S0010440X19300446 kostenfrei https://doaj.org/toc/0010-440X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 94 2019 - |
spelling |
10.1016/j.comppsych.2019.152121 doi (DE-627)DOAJ032173539 (DE-599)DOAJ857c0a71fdc3462aa355be763bb8cac3 DE-627 ger DE-627 rakwb eng RC435-571 Lin Wan verfasserin aut Sex-specific effects of methylenetetrahydrofolate reductase polymorphisms on schizophrenia with methylation changes 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Methylenetetrahydrofolate reductase (MTHFR) is the critical enzyme in biotransformation. The polymorphism of MTHFR is a risk factor for schizophrenia. However, whether the MTHFR polymorphism is associated with schizophrenia disease phenotypes and what is the underlying mechanism of MTHFR polymorphism in schizophrenia is under-investigated. In this study, we aim to verify the correlation between MTHFR polymorphisms and clinical features of schizophrenia, while exploring the differential genomic methylation and disease related genes as the potential targets for schizophrenia. Method: 242 patients of schizophrenia and 234 matched healthy controls were enrolled in this study. Polymorphisms of MTHFR from three sites (C677T, A1298C, G1793A) were examined by Taqman fluorescence probe method in leukocytes from all subjects. The positive and negative syndrome scale (PANSS), trail making test (TMT) and Clinical Global Impression (CGI) were checked on patients. Genomic methylation was tested and analyzed in fields of differential methylation positions (DMPs) and enrichment of genes that are potentially related to schizophrenia. Results: Schizophrenic patients showed higher frequency of MTHFR polymorphisms at both single and multiple sites than healthy controls. Our data also showed that MTHFR C677T and multiple-site polymorphisms were positively correlated with PANSS positive rating, not negative score in male schizophrenia patients. Furthermore, while a significant reduction of global DNA methylation level was observed in schizophrenic patients, we also identified several genes which differentiated between schizophrenia and healthy controls at methylation levels. Conclusions: This is a pilot study revealing that MTHFR polymorphisms at both single and multiple sites are related to the risk of schizophrenia and positive symptom of the disease. The risk of MTHFR polymorphism in schizophrenia and the clinical symptoms was only significant in male patients. While the sex-specific risk of MTHFR in schizophrenia is new and the reasons remain unanswered. Our methylation analysis suggested that there was significant hypomethylation of genomic DNA in schizophrenia patients with no sex difference. The correlation between MTHFR polymorphism and schizophrenia may attribute to the change of DNA methylation level, and some certain genes could be potential research objects for MTHFR effects on schizophrenia. Keywords: MTHFR, Schizophrenia, Polymorphism, Symptom, Methylation Psychiatry Guofu Zhang verfasserin aut Min Liu verfasserin aut Chuanyue Wang verfasserin aut Yuhong Li verfasserin aut Rena Li verfasserin aut In Comprehensive Psychiatry Elsevier, 2019 94(2019), Seite - (DE-627)330080377 (DE-600)2049049-5 15328384 nnns volume:94 year:2019 pages:- https://doi.org/10.1016/j.comppsych.2019.152121 kostenfrei https://doaj.org/article/857c0a71fdc3462aa355be763bb8cac3 kostenfrei http://www.sciencedirect.com/science/article/pii/S0010440X19300446 kostenfrei https://doaj.org/toc/0010-440X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 94 2019 - |
allfields_unstemmed |
10.1016/j.comppsych.2019.152121 doi (DE-627)DOAJ032173539 (DE-599)DOAJ857c0a71fdc3462aa355be763bb8cac3 DE-627 ger DE-627 rakwb eng RC435-571 Lin Wan verfasserin aut Sex-specific effects of methylenetetrahydrofolate reductase polymorphisms on schizophrenia with methylation changes 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Methylenetetrahydrofolate reductase (MTHFR) is the critical enzyme in biotransformation. The polymorphism of MTHFR is a risk factor for schizophrenia. However, whether the MTHFR polymorphism is associated with schizophrenia disease phenotypes and what is the underlying mechanism of MTHFR polymorphism in schizophrenia is under-investigated. In this study, we aim to verify the correlation between MTHFR polymorphisms and clinical features of schizophrenia, while exploring the differential genomic methylation and disease related genes as the potential targets for schizophrenia. Method: 242 patients of schizophrenia and 234 matched healthy controls were enrolled in this study. Polymorphisms of MTHFR from three sites (C677T, A1298C, G1793A) were examined by Taqman fluorescence probe method in leukocytes from all subjects. The positive and negative syndrome scale (PANSS), trail making test (TMT) and Clinical Global Impression (CGI) were checked on patients. Genomic methylation was tested and analyzed in fields of differential methylation positions (DMPs) and enrichment of genes that are potentially related to schizophrenia. Results: Schizophrenic patients showed higher frequency of MTHFR polymorphisms at both single and multiple sites than healthy controls. Our data also showed that MTHFR C677T and multiple-site polymorphisms were positively correlated with PANSS positive rating, not negative score in male schizophrenia patients. Furthermore, while a significant reduction of global DNA methylation level was observed in schizophrenic patients, we also identified several genes which differentiated between schizophrenia and healthy controls at methylation levels. Conclusions: This is a pilot study revealing that MTHFR polymorphisms at both single and multiple sites are related to the risk of schizophrenia and positive symptom of the disease. The risk of MTHFR polymorphism in schizophrenia and the clinical symptoms was only significant in male patients. While the sex-specific risk of MTHFR in schizophrenia is new and the reasons remain unanswered. Our methylation analysis suggested that there was significant hypomethylation of genomic DNA in schizophrenia patients with no sex difference. The correlation between MTHFR polymorphism and schizophrenia may attribute to the change of DNA methylation level, and some certain genes could be potential research objects for MTHFR effects on schizophrenia. Keywords: MTHFR, Schizophrenia, Polymorphism, Symptom, Methylation Psychiatry Guofu Zhang verfasserin aut Min Liu verfasserin aut Chuanyue Wang verfasserin aut Yuhong Li verfasserin aut Rena Li verfasserin aut In Comprehensive Psychiatry Elsevier, 2019 94(2019), Seite - (DE-627)330080377 (DE-600)2049049-5 15328384 nnns volume:94 year:2019 pages:- https://doi.org/10.1016/j.comppsych.2019.152121 kostenfrei https://doaj.org/article/857c0a71fdc3462aa355be763bb8cac3 kostenfrei http://www.sciencedirect.com/science/article/pii/S0010440X19300446 kostenfrei https://doaj.org/toc/0010-440X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 94 2019 - |
allfieldsGer |
10.1016/j.comppsych.2019.152121 doi (DE-627)DOAJ032173539 (DE-599)DOAJ857c0a71fdc3462aa355be763bb8cac3 DE-627 ger DE-627 rakwb eng RC435-571 Lin Wan verfasserin aut Sex-specific effects of methylenetetrahydrofolate reductase polymorphisms on schizophrenia with methylation changes 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background: Methylenetetrahydrofolate reductase (MTHFR) is the critical enzyme in biotransformation. The polymorphism of MTHFR is a risk factor for schizophrenia. However, whether the MTHFR polymorphism is associated with schizophrenia disease phenotypes and what is the underlying mechanism of MTHFR polymorphism in schizophrenia is under-investigated. In this study, we aim to verify the correlation between MTHFR polymorphisms and clinical features of schizophrenia, while exploring the differential genomic methylation and disease related genes as the potential targets for schizophrenia. Method: 242 patients of schizophrenia and 234 matched healthy controls were enrolled in this study. Polymorphisms of MTHFR from three sites (C677T, A1298C, G1793A) were examined by Taqman fluorescence probe method in leukocytes from all subjects. The positive and negative syndrome scale (PANSS), trail making test (TMT) and Clinical Global Impression (CGI) were checked on patients. Genomic methylation was tested and analyzed in fields of differential methylation positions (DMPs) and enrichment of genes that are potentially related to schizophrenia. Results: Schizophrenic patients showed higher frequency of MTHFR polymorphisms at both single and multiple sites than healthy controls. Our data also showed that MTHFR C677T and multiple-site polymorphisms were positively correlated with PANSS positive rating, not negative score in male schizophrenia patients. Furthermore, while a significant reduction of global DNA methylation level was observed in schizophrenic patients, we also identified several genes which differentiated between schizophrenia and healthy controls at methylation levels. Conclusions: This is a pilot study revealing that MTHFR polymorphisms at both single and multiple sites are related to the risk of schizophrenia and positive symptom of the disease. The risk of MTHFR polymorphism in schizophrenia and the clinical symptoms was only significant in male patients. While the sex-specific risk of MTHFR in schizophrenia is new and the reasons remain unanswered. Our methylation analysis suggested that there was significant hypomethylation of genomic DNA in schizophrenia patients with no sex difference. The correlation between MTHFR polymorphism and schizophrenia may attribute to the change of DNA methylation level, and some certain genes could be potential research objects for MTHFR effects on schizophrenia. Keywords: MTHFR, Schizophrenia, Polymorphism, Symptom, Methylation Psychiatry Guofu Zhang verfasserin aut Min Liu verfasserin aut Chuanyue Wang verfasserin aut Yuhong Li verfasserin aut Rena Li verfasserin aut In Comprehensive Psychiatry Elsevier, 2019 94(2019), Seite - (DE-627)330080377 (DE-600)2049049-5 15328384 nnns volume:94 year:2019 pages:- https://doi.org/10.1016/j.comppsych.2019.152121 kostenfrei https://doaj.org/article/857c0a71fdc3462aa355be763bb8cac3 kostenfrei http://www.sciencedirect.com/science/article/pii/S0010440X19300446 kostenfrei https://doaj.org/toc/0010-440X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2025 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 94 2019 - |
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Sex-specific effects of methylenetetrahydrofolate reductase polymorphisms on schizophrenia with methylation changes |
abstract |
Background: Methylenetetrahydrofolate reductase (MTHFR) is the critical enzyme in biotransformation. The polymorphism of MTHFR is a risk factor for schizophrenia. However, whether the MTHFR polymorphism is associated with schizophrenia disease phenotypes and what is the underlying mechanism of MTHFR polymorphism in schizophrenia is under-investigated. In this study, we aim to verify the correlation between MTHFR polymorphisms and clinical features of schizophrenia, while exploring the differential genomic methylation and disease related genes as the potential targets for schizophrenia. Method: 242 patients of schizophrenia and 234 matched healthy controls were enrolled in this study. Polymorphisms of MTHFR from three sites (C677T, A1298C, G1793A) were examined by Taqman fluorescence probe method in leukocytes from all subjects. The positive and negative syndrome scale (PANSS), trail making test (TMT) and Clinical Global Impression (CGI) were checked on patients. Genomic methylation was tested and analyzed in fields of differential methylation positions (DMPs) and enrichment of genes that are potentially related to schizophrenia. Results: Schizophrenic patients showed higher frequency of MTHFR polymorphisms at both single and multiple sites than healthy controls. Our data also showed that MTHFR C677T and multiple-site polymorphisms were positively correlated with PANSS positive rating, not negative score in male schizophrenia patients. Furthermore, while a significant reduction of global DNA methylation level was observed in schizophrenic patients, we also identified several genes which differentiated between schizophrenia and healthy controls at methylation levels. Conclusions: This is a pilot study revealing that MTHFR polymorphisms at both single and multiple sites are related to the risk of schizophrenia and positive symptom of the disease. The risk of MTHFR polymorphism in schizophrenia and the clinical symptoms was only significant in male patients. While the sex-specific risk of MTHFR in schizophrenia is new and the reasons remain unanswered. Our methylation analysis suggested that there was significant hypomethylation of genomic DNA in schizophrenia patients with no sex difference. The correlation between MTHFR polymorphism and schizophrenia may attribute to the change of DNA methylation level, and some certain genes could be potential research objects for MTHFR effects on schizophrenia. Keywords: MTHFR, Schizophrenia, Polymorphism, Symptom, Methylation |
abstractGer |
Background: Methylenetetrahydrofolate reductase (MTHFR) is the critical enzyme in biotransformation. The polymorphism of MTHFR is a risk factor for schizophrenia. However, whether the MTHFR polymorphism is associated with schizophrenia disease phenotypes and what is the underlying mechanism of MTHFR polymorphism in schizophrenia is under-investigated. In this study, we aim to verify the correlation between MTHFR polymorphisms and clinical features of schizophrenia, while exploring the differential genomic methylation and disease related genes as the potential targets for schizophrenia. Method: 242 patients of schizophrenia and 234 matched healthy controls were enrolled in this study. Polymorphisms of MTHFR from three sites (C677T, A1298C, G1793A) were examined by Taqman fluorescence probe method in leukocytes from all subjects. The positive and negative syndrome scale (PANSS), trail making test (TMT) and Clinical Global Impression (CGI) were checked on patients. Genomic methylation was tested and analyzed in fields of differential methylation positions (DMPs) and enrichment of genes that are potentially related to schizophrenia. Results: Schizophrenic patients showed higher frequency of MTHFR polymorphisms at both single and multiple sites than healthy controls. Our data also showed that MTHFR C677T and multiple-site polymorphisms were positively correlated with PANSS positive rating, not negative score in male schizophrenia patients. Furthermore, while a significant reduction of global DNA methylation level was observed in schizophrenic patients, we also identified several genes which differentiated between schizophrenia and healthy controls at methylation levels. Conclusions: This is a pilot study revealing that MTHFR polymorphisms at both single and multiple sites are related to the risk of schizophrenia and positive symptom of the disease. The risk of MTHFR polymorphism in schizophrenia and the clinical symptoms was only significant in male patients. While the sex-specific risk of MTHFR in schizophrenia is new and the reasons remain unanswered. Our methylation analysis suggested that there was significant hypomethylation of genomic DNA in schizophrenia patients with no sex difference. The correlation between MTHFR polymorphism and schizophrenia may attribute to the change of DNA methylation level, and some certain genes could be potential research objects for MTHFR effects on schizophrenia. Keywords: MTHFR, Schizophrenia, Polymorphism, Symptom, Methylation |
abstract_unstemmed |
Background: Methylenetetrahydrofolate reductase (MTHFR) is the critical enzyme in biotransformation. The polymorphism of MTHFR is a risk factor for schizophrenia. However, whether the MTHFR polymorphism is associated with schizophrenia disease phenotypes and what is the underlying mechanism of MTHFR polymorphism in schizophrenia is under-investigated. In this study, we aim to verify the correlation between MTHFR polymorphisms and clinical features of schizophrenia, while exploring the differential genomic methylation and disease related genes as the potential targets for schizophrenia. Method: 242 patients of schizophrenia and 234 matched healthy controls were enrolled in this study. Polymorphisms of MTHFR from three sites (C677T, A1298C, G1793A) were examined by Taqman fluorescence probe method in leukocytes from all subjects. The positive and negative syndrome scale (PANSS), trail making test (TMT) and Clinical Global Impression (CGI) were checked on patients. Genomic methylation was tested and analyzed in fields of differential methylation positions (DMPs) and enrichment of genes that are potentially related to schizophrenia. Results: Schizophrenic patients showed higher frequency of MTHFR polymorphisms at both single and multiple sites than healthy controls. Our data also showed that MTHFR C677T and multiple-site polymorphisms were positively correlated with PANSS positive rating, not negative score in male schizophrenia patients. Furthermore, while a significant reduction of global DNA methylation level was observed in schizophrenic patients, we also identified several genes which differentiated between schizophrenia and healthy controls at methylation levels. Conclusions: This is a pilot study revealing that MTHFR polymorphisms at both single and multiple sites are related to the risk of schizophrenia and positive symptom of the disease. The risk of MTHFR polymorphism in schizophrenia and the clinical symptoms was only significant in male patients. While the sex-specific risk of MTHFR in schizophrenia is new and the reasons remain unanswered. Our methylation analysis suggested that there was significant hypomethylation of genomic DNA in schizophrenia patients with no sex difference. The correlation between MTHFR polymorphism and schizophrenia may attribute to the change of DNA methylation level, and some certain genes could be potential research objects for MTHFR effects on schizophrenia. Keywords: MTHFR, Schizophrenia, Polymorphism, Symptom, Methylation |
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title_short |
Sex-specific effects of methylenetetrahydrofolate reductase polymorphisms on schizophrenia with methylation changes |
url |
https://doi.org/10.1016/j.comppsych.2019.152121 https://doaj.org/article/857c0a71fdc3462aa355be763bb8cac3 http://www.sciencedirect.com/science/article/pii/S0010440X19300446 https://doaj.org/toc/0010-440X |
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Guofu Zhang Min Liu Chuanyue Wang Yuhong Li Rena Li |
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up_date |
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