Male-specific association between dopamine receptor D4 gene methylation and schizophrenia
The goal of our study was to investigate whether DRD4 gene DNA methylation played an important role in the susceptibility of Han Chinese SCZ. Using the bisulphite pyrosequencing technology, DNA methylation levels of 6 CpG dinucleotides in DRD4 CpG island were measured among 30 paranoid SCZ patients,...
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| creator | Cheng, Jia Wang, Yunliang Zhou, Kena Wang, Lingyan Li, Jinfeng Zhuang, Qidong Xu, Xuting Xu, Leiting Zhang, Kai Dai, Dongjun Zheng, Rongjiong Li, Guangxue Zhang, Aiping Gao, Shugui Duan, Shiwei |
| description | The goal of our study was to investigate whether DRD4 gene DNA methylation played an important role in the susceptibility of Han Chinese SCZ.
Using the bisulphite pyrosequencing technology, DNA methylation levels of 6 CpG dinucleotides in DRD4 CpG island were measured among 30 paranoid SCZ patients, 30 undifferentiated SCZ patients, and 30 age- and gender-matched healthy controls.
Strong correlation was observed among the six CpG sites (r>0.5, P |
| doi_str_mv | 10.1371/journal.pone.0089128 |
| format | Article |
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Using the bisulphite pyrosequencing technology, DNA methylation levels of 6 CpG dinucleotides in DRD4 CpG island were measured among 30 paranoid SCZ patients, 30 undifferentiated SCZ patients, and 30 age- and gender-matched healthy controls.
Strong correlation was observed among the six CpG sites (r>0.5, P<0.01), thus average methylation levels were applied thereafter. Our results indicated that there was a significant association between DRD4 methylation and the risk of SCZ (P = 0.003), although there was no significant difference in DRD4 methylation between the two SCZ subtypes (P = 0.670). A breakdown analysis by gender showed that the significant association of DRD4 methylation and SCZ was driven by males (P<0.001) but not by females (P = 0.835). DRD4 methylation was significantly associated with p300 in male SCZ patients (r = -0.543, P = 0.005) but not in female SCZ patients (r = 0.110, P = 0.599). Moreover, receiver operating characteristic (ROC) curves showed DRD4 methylation was able to predict the status of SCZ in males [area under curve (AUC) = 0.832, P = 0.002] but not in females (AUC = 0.483, P = 0.876). Finally, a further expression experiment showed that DRD4 methylation in the gene body was positively associated with gene expression, although the exact mechanism of gene regulation remained unknown for this interesting DRD4 methylation.
The gender disparity in the DRD4 DNA methylation provides novel insights into the pathogenesis of SCZ.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0089128</identifier><identifier>PMID: 24586542</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adolescent ; Adult ; Analysis ; Antipsychotics ; Behavior disorders ; Biology ; Cardiovascular disease ; Child ; CpG islands ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Dopamine ; Dopamine D4 receptors ; Dopamine receptors ; Drug abuse ; Epigenetics ; Event-related potentials ; Female ; Females ; Gender ; Gene expression ; Gene regulation ; Genes ; Genetic Association Studies ; Genetic Predisposition to Disease ; Hospitals ; Humans ; Laboratories ; Linkage Disequilibrium ; Male ; Males ; Medicine ; Mental disorders ; Methylation ; Pathogenesis ; Patients ; Phenols (Class of compounds) ; Promoter Regions, Genetic ; Psychiatry ; Psychotropic drugs ; Receptors, Dopamine D4 - genetics ; Receptors, Dopamine D4 - metabolism ; Schizophrenia ; Schizophrenia - epidemiology ; Schizophrenia - genetics ; Sex Factors ; Young Adult</subject><ispartof>PloS one, 2014-02, Vol.9 (2), p.e89128-e89128</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Cheng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Cheng et al 2014 Cheng et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-45d1269ce8aef33c9ba40fcaea1a1d1f5e93b0048f42e09a704c01fff88e70313</citedby><cites>FETCH-LOGICAL-c758t-45d1269ce8aef33c9ba40fcaea1a1d1f5e93b0048f42e09a704c01fff88e70313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929639/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929639/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24586542$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Hu, Valerie W.</contributor><creatorcontrib>Cheng, Jia</creatorcontrib><creatorcontrib>Wang, Yunliang</creatorcontrib><creatorcontrib>Zhou, Kena</creatorcontrib><creatorcontrib>Wang, Lingyan</creatorcontrib><creatorcontrib>Li, Jinfeng</creatorcontrib><creatorcontrib>Zhuang, Qidong</creatorcontrib><creatorcontrib>Xu, Xuting</creatorcontrib><creatorcontrib>Xu, Leiting</creatorcontrib><creatorcontrib>Zhang, Kai</creatorcontrib><creatorcontrib>Dai, Dongjun</creatorcontrib><creatorcontrib>Zheng, Rongjiong</creatorcontrib><creatorcontrib>Li, Guangxue</creatorcontrib><creatorcontrib>Zhang, Aiping</creatorcontrib><creatorcontrib>Gao, Shugui</creatorcontrib><creatorcontrib>Duan, Shiwei</creatorcontrib><title>Male-specific association between dopamine receptor D4 gene methylation and schizophrenia</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The goal of our study was to investigate whether DRD4 gene DNA methylation played an important role in the susceptibility of Han Chinese SCZ.
Using the bisulphite pyrosequencing technology, DNA methylation levels of 6 CpG dinucleotides in DRD4 CpG island were measured among 30 paranoid SCZ patients, 30 undifferentiated SCZ patients, and 30 age- and gender-matched healthy controls.
Strong correlation was observed among the six CpG sites (r>0.5, P<0.01), thus average methylation levels were applied thereafter. Our results indicated that there was a significant association between DRD4 methylation and the risk of SCZ (P = 0.003), although there was no significant difference in DRD4 methylation between the two SCZ subtypes (P = 0.670). A breakdown analysis by gender showed that the significant association of DRD4 methylation and SCZ was driven by males (P<0.001) but not by females (P = 0.835). DRD4 methylation was significantly associated with p300 in male SCZ patients (r = -0.543, P = 0.005) but not in female SCZ patients (r = 0.110, P = 0.599). Moreover, receiver operating characteristic (ROC) curves showed DRD4 methylation was able to predict the status of SCZ in males [area under curve (AUC) = 0.832, P = 0.002] but not in females (AUC = 0.483, P = 0.876). Finally, a further expression experiment showed that DRD4 methylation in the gene body was positively associated with gene expression, although the exact mechanism of gene regulation remained unknown for this interesting DRD4 methylation.
The gender disparity in the DRD4 DNA methylation provides novel insights into the pathogenesis of SCZ.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Analysis</subject><subject>Antipsychotics</subject><subject>Behavior disorders</subject><subject>Biology</subject><subject>Cardiovascular disease</subject><subject>Child</subject><subject>CpG islands</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Dopamine</subject><subject>Dopamine D4 receptors</subject><subject>Dopamine receptors</subject><subject>Drug abuse</subject><subject>Epigenetics</subject><subject>Event-related potentials</subject><subject>Female</subject><subject>Females</subject><subject>Gender</subject><subject>Gene expression</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Genetic Association Studies</subject><subject>Genetic Predisposition to Disease</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Laboratories</subject><subject>Linkage Disequilibrium</subject><subject>Male</subject><subject>Males</subject><subject>Medicine</subject><subject>Mental disorders</subject><subject>Methylation</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Phenols (Class of compounds)</subject><subject>Promoter Regions, Genetic</subject><subject>Psychiatry</subject><subject>Psychotropic drugs</subject><subject>Receptors, Dopamine D4 - genetics</subject><subject>Receptors, Dopamine D4 - metabolism</subject><subject>Schizophrenia</subject><subject>Schizophrenia - epidemiology</subject><subject>Schizophrenia - genetics</subject><subject>Sex Factors</subject><subject>Young 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association between dopamine receptor D4 gene methylation and schizophrenia</title><author>Cheng, Jia ; Wang, Yunliang ; Zhou, Kena ; Wang, Lingyan ; Li, Jinfeng ; Zhuang, Qidong ; Xu, Xuting ; Xu, Leiting ; Zhang, Kai ; Dai, Dongjun ; Zheng, Rongjiong ; Li, Guangxue ; Zhang, Aiping ; Gao, Shugui ; Duan, Shiwei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-45d1269ce8aef33c9ba40fcaea1a1d1f5e93b0048f42e09a704c01fff88e70313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Analysis</topic><topic>Antipsychotics</topic><topic>Behavior disorders</topic><topic>Biology</topic><topic>Cardiovascular disease</topic><topic>Child</topic><topic>CpG islands</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Dopamine</topic><topic>Dopamine D4 receptors</topic><topic>Dopamine 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W.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Male-specific association between dopamine receptor D4 gene methylation and schizophrenia</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-02-19</date><risdate>2014</risdate><volume>9</volume><issue>2</issue><spage>e89128</spage><epage>e89128</epage><pages>e89128-e89128</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The goal of our study was to investigate whether DRD4 gene DNA methylation played an important role in the susceptibility of Han Chinese SCZ.
Using the bisulphite pyrosequencing technology, DNA methylation levels of 6 CpG dinucleotides in DRD4 CpG island were measured among 30 paranoid SCZ patients, 30 undifferentiated SCZ patients, and 30 age- and gender-matched healthy controls.
Strong correlation was observed among the six CpG sites (r>0.5, P<0.01), thus average methylation levels were applied thereafter. Our results indicated that there was a significant association between DRD4 methylation and the risk of SCZ (P = 0.003), although there was no significant difference in DRD4 methylation between the two SCZ subtypes (P = 0.670). A breakdown analysis by gender showed that the significant association of DRD4 methylation and SCZ was driven by males (P<0.001) but not by females (P = 0.835). DRD4 methylation was significantly associated with p300 in male SCZ patients (r = -0.543, P = 0.005) but not in female SCZ patients (r = 0.110, P = 0.599). Moreover, receiver operating characteristic (ROC) curves showed DRD4 methylation was able to predict the status of SCZ in males [area under curve (AUC) = 0.832, P = 0.002] but not in females (AUC = 0.483, P = 0.876). Finally, a further expression experiment showed that DRD4 methylation in the gene body was positively associated with gene expression, although the exact mechanism of gene regulation remained unknown for this interesting DRD4 methylation.
The gender disparity in the DRD4 DNA methylation provides novel insights into the pathogenesis of SCZ.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24586542</pmid><doi>10.1371/journal.pone.0089128</doi><tpages>e89128</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adolescent Adult Analysis Antipsychotics Behavior disorders Biology Cardiovascular disease Child CpG islands Deoxyribonucleic acid DNA DNA Methylation Dopamine Dopamine D4 receptors Dopamine receptors Drug abuse Epigenetics Event-related potentials Female Females Gender Gene expression Gene regulation Genes Genetic Association Studies Genetic Predisposition to Disease Hospitals Humans Laboratories Linkage Disequilibrium Male Males Medicine Mental disorders Methylation Pathogenesis Patients Phenols (Class of compounds) Promoter Regions, Genetic Psychiatry Psychotropic drugs Receptors, Dopamine D4 - genetics Receptors, Dopamine D4 - metabolism Schizophrenia Schizophrenia - epidemiology Schizophrenia - genetics Sex Factors Young Adult |
| title | Male-specific association between dopamine receptor D4 gene methylation and schizophrenia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-19T00%3A19%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Male-specific%20association%20between%20dopamine%20receptor%20D4%20gene%20methylation%20and%20schizophrenia&rft.jtitle=PloS%20one&rft.au=Cheng,%20Jia&rft.date=2014-02-19&rft.volume=9&rft.issue=2&rft.spage=e89128&rft.epage=e89128&rft.pages=e89128-e89128&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0089128&rft_dat=%3Cgale_plos_%3EA478798981%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1500410805&rft_id=info:pmid/24586542&rft_galeid=A478798981&rft_doaj_id=oai_doaj_org_article_fb91755c40de456d860659423b1ce1f5&rfr_iscdi=true |