Association of polymorphisms in RGS4 and expression of RGS transcripts in the brains of human alcoholics
Abstract Chronic alcoholism leads to neurotoxic effects in the central nervous system. Neuroadaptive changes in the brain may lead to tolerance to, and dependence on, alcohol as a result of alterations in synaptic complexity. G-proteins are negatively regulated by RGS proteins, which are integral to...
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| description | Abstract Chronic alcoholism leads to neurotoxic effects in the central nervous system. Neuroadaptive changes in the brain may lead to tolerance to, and dependence on, alcohol as a result of alterations in synaptic complexity. G-proteins are negatively regulated by RGS proteins, which are integral to many neural pathways that include neurotransmission, hormonal responses, and chemotactic signals. These considerations, together with findings from microarray analyses of human autopsy brain, suggest that proteins involved in G-protein signalling, specifically the RGS protein family, may play an important role in the functioning of neural systems that are affected by chronic alcohol abuse. We used Real Time PCR to measure the expression of two members of the RGS family, RGS4 and RGS7, in the superior frontal gyrus and primary motor cortex from alcoholic and non-alcoholic cases. Overall, cirrhotic alcoholics had lower expression levels of RGS4 mRNA than controls and non-cirrhotic alcoholics. We also report that the four RGS4 SNPs (SNP1, 4, 7 and 18) may be associated with alcoholism in European Caucasians at the haplotype level. The haplotype T-C-G (SNP1-4-18) may exert a protective effect against alcoholism. |
| doi_str_mv | 10.1016/j.brainres.2010.04.049 |
| format | Article |
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Neuroadaptive changes in the brain may lead to tolerance to, and dependence on, alcohol as a result of alterations in synaptic complexity. G-proteins are negatively regulated by RGS proteins, which are integral to many neural pathways that include neurotransmission, hormonal responses, and chemotactic signals. These considerations, together with findings from microarray analyses of human autopsy brain, suggest that proteins involved in G-protein signalling, specifically the RGS protein family, may play an important role in the functioning of neural systems that are affected by chronic alcohol abuse. We used Real Time PCR to measure the expression of two members of the RGS family, RGS4 and RGS7, in the superior frontal gyrus and primary motor cortex from alcoholic and non-alcoholic cases. Overall, cirrhotic alcoholics had lower expression levels of RGS4 mRNA than controls and non-cirrhotic alcoholics. We also report that the four RGS4 SNPs (SNP1, 4, 7 and 18) may be associated with alcoholism in European Caucasians at the haplotype level. The haplotype T-C-G (SNP1-4-18) may exert a protective effect against alcoholism.</description><identifier>ISSN: 0006-8993</identifier><identifier>EISSN: 1872-6240</identifier><identifier>DOI: 10.1016/j.brainres.2010.04.049</identifier><identifier>PMID: 20430014</identifier><identifier>CODEN: BRREAP</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Addictive behaviors ; Adult and adolescent clinical studies ; Aged ; Alcoholism ; Alcoholism - genetics ; Alcoholism - metabolism ; Alcoholism and acute alcohol poisoning ; Biological and medical sciences ; Brain Chemistry - genetics ; Cirrhosis ; Female ; G-protein signaling ; Gene Expression Regulation - physiology ; Genetic Predisposition to Disease - genetics ; GTP-Binding Proteins - genetics ; GTP-Binding Proteins - metabolism ; Humans ; Liver Cirrhosis, Alcoholic - genetics ; Liver Cirrhosis, Alcoholic - metabolism ; Male ; Medical sciences ; Middle Aged ; Neurology ; Polymorphism, Genetic - genetics ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Real Time PCR ; RGS Proteins - genetics ; RGS Proteins - metabolism ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; Sex differences ; Toxicology</subject><ispartof>Brain research, 2010-06, Vol.1340, p.1-9</ispartof><rights>Elsevier B.V.</rights><rights>2010 Elsevier B.V.</rights><rights>2015 INIST-CNRS</rights><rights>(c) 2010 Elsevier B.V. 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Neuroadaptive changes in the brain may lead to tolerance to, and dependence on, alcohol as a result of alterations in synaptic complexity. G-proteins are negatively regulated by RGS proteins, which are integral to many neural pathways that include neurotransmission, hormonal responses, and chemotactic signals. These considerations, together with findings from microarray analyses of human autopsy brain, suggest that proteins involved in G-protein signalling, specifically the RGS protein family, may play an important role in the functioning of neural systems that are affected by chronic alcohol abuse. We used Real Time PCR to measure the expression of two members of the RGS family, RGS4 and RGS7, in the superior frontal gyrus and primary motor cortex from alcoholic and non-alcoholic cases. Overall, cirrhotic alcoholics had lower expression levels of RGS4 mRNA than controls and non-cirrhotic alcoholics. We also report that the four RGS4 SNPs (SNP1, 4, 7 and 18) may be associated with alcoholism in European Caucasians at the haplotype level. The haplotype T-C-G (SNP1-4-18) may exert a protective effect against alcoholism.</description><subject>Addictive behaviors</subject><subject>Adult and adolescent clinical studies</subject><subject>Aged</subject><subject>Alcoholism</subject><subject>Alcoholism - genetics</subject><subject>Alcoholism - metabolism</subject><subject>Alcoholism and acute alcohol poisoning</subject><subject>Biological and medical sciences</subject><subject>Brain Chemistry - genetics</subject><subject>Cirrhosis</subject><subject>Female</subject><subject>G-protein signaling</subject><subject>Gene Expression Regulation - physiology</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>GTP-Binding Proteins - genetics</subject><subject>GTP-Binding Proteins - metabolism</subject><subject>Humans</subject><subject>Liver Cirrhosis, Alcoholic - genetics</subject><subject>Liver Cirrhosis, Alcoholic - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neurology</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Real Time PCR</subject><subject>RGS Proteins - genetics</subject><subject>RGS Proteins - metabolism</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - genetics</subject><subject>Sex differences</subject><subject>Toxicology</subject><issn>0006-8993</issn><issn>1872-6240</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkktv1DAQxyMEokvhK1S5IE67jB95XSqqCgpSJSQKZ8txxsRLYgdPtup-e5zutjwuSCPZHv_moflPlp0x2DBg5dvtpo3a-Yi04ZCcIJM1T7IVqyu-LrmEp9kKAMp13TTiJHtBtE1PIRp4np1wkAKAyVXWXxAF4_Tsgs-Dzacw7McQp97RSLnz-ZerG5lr3-V4N6VqdOSSO5-j9mSim-Z7cu4xv2-KFqDfjdrnejChD4Mz9DJ7ZvVA-Op4nmbfPrz_evlxff356tPlxfXaFHU1r43uClZaELxjramt7qCxBrHVom6k4ULwysoSrTWysqKw2qBA3lUtVoWEUpxm54e8064dsTPoU5uDmqIbddyroJ36-8e7Xn0Pt4o3wGXRpARvjgli-LlDmtXoyOAwaI9hR6quqqJihVjI8kCaGIgi2scqDNSiktqqB5XUopICmWwJPPuzx8ewB1kS8PoIaDJ6sGnQxtFvjjcSeAGJe3fgME301mFUZBx6g52LaGbVBff_Xs7_SWEG512q-gP3SNuwiz7ppZgirkDdLDu1rBRLl0aWlfgF7SLMCg</recordid><startdate>20100622</startdate><enddate>20100622</enddate><creator>Ho, Ada M.-C</creator><creator>MacKay, Rachel K</creator><creator>Dodd, Peter R</creator><creator>Lewohl, Joanne M</creator><general>Elsevier B.V</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>5PM</scope></search><sort><creationdate>20100622</creationdate><title>Association of polymorphisms in RGS4 and expression of RGS transcripts in the brains of human alcoholics</title><author>Ho, Ada M.-C ; MacKay, Rachel K ; Dodd, Peter R ; Lewohl, Joanne M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c587t-cad516f032d1bc8fad09fceeba3894c23327f46effc47f35face3e2d7be754063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Addictive behaviors</topic><topic>Adult and adolescent clinical studies</topic><topic>Aged</topic><topic>Alcoholism</topic><topic>Alcoholism - genetics</topic><topic>Alcoholism - metabolism</topic><topic>Alcoholism and acute alcohol poisoning</topic><topic>Biological and medical sciences</topic><topic>Brain Chemistry - genetics</topic><topic>Cirrhosis</topic><topic>Female</topic><topic>G-protein signaling</topic><topic>Gene Expression Regulation - physiology</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>GTP-Binding Proteins - genetics</topic><topic>GTP-Binding Proteins - metabolism</topic><topic>Humans</topic><topic>Liver Cirrhosis, Alcoholic - genetics</topic><topic>Liver Cirrhosis, Alcoholic - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neurology</topic><topic>Polymorphism, Genetic - genetics</topic><topic>Psychology. Psychoanalysis. Psychiatry</topic><topic>Psychopathology. Psychiatry</topic><topic>Real Time PCR</topic><topic>RGS Proteins - genetics</topic><topic>RGS Proteins - metabolism</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - genetics</topic><topic>Sex differences</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ho, Ada M.-C</creatorcontrib><creatorcontrib>MacKay, Rachel K</creatorcontrib><creatorcontrib>Dodd, Peter R</creatorcontrib><creatorcontrib>Lewohl, Joanne M</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ho, Ada M.-C</au><au>MacKay, Rachel K</au><au>Dodd, Peter R</au><au>Lewohl, Joanne M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association of polymorphisms in RGS4 and expression of RGS transcripts in the brains of human alcoholics</atitle><jtitle>Brain research</jtitle><addtitle>Brain Res</addtitle><date>2010-06-22</date><risdate>2010</risdate><volume>1340</volume><spage>1</spage><epage>9</epage><pages>1-9</pages><issn>0006-8993</issn><eissn>1872-6240</eissn><coden>BRREAP</coden><abstract>Abstract Chronic alcoholism leads to neurotoxic effects in the central nervous system. Neuroadaptive changes in the brain may lead to tolerance to, and dependence on, alcohol as a result of alterations in synaptic complexity. G-proteins are negatively regulated by RGS proteins, which are integral to many neural pathways that include neurotransmission, hormonal responses, and chemotactic signals. These considerations, together with findings from microarray analyses of human autopsy brain, suggest that proteins involved in G-protein signalling, specifically the RGS protein family, may play an important role in the functioning of neural systems that are affected by chronic alcohol abuse. We used Real Time PCR to measure the expression of two members of the RGS family, RGS4 and RGS7, in the superior frontal gyrus and primary motor cortex from alcoholic and non-alcoholic cases. Overall, cirrhotic alcoholics had lower expression levels of RGS4 mRNA than controls and non-cirrhotic alcoholics. We also report that the four RGS4 SNPs (SNP1, 4, 7 and 18) may be associated with alcoholism in European Caucasians at the haplotype level. The haplotype T-C-G (SNP1-4-18) may exert a protective effect against alcoholism.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>20430014</pmid><doi>10.1016/j.brainres.2010.04.049</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Addictive behaviors Adult and adolescent clinical studies Aged Alcoholism Alcoholism - genetics Alcoholism - metabolism Alcoholism and acute alcohol poisoning Biological and medical sciences Brain Chemistry - genetics Cirrhosis Female G-protein signaling Gene Expression Regulation - physiology Genetic Predisposition to Disease - genetics GTP-Binding Proteins - genetics GTP-Binding Proteins - metabolism Humans Liver Cirrhosis, Alcoholic - genetics Liver Cirrhosis, Alcoholic - metabolism Male Medical sciences Middle Aged Neurology Polymorphism, Genetic - genetics Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Real Time PCR RGS Proteins - genetics RGS Proteins - metabolism RNA, Messenger - biosynthesis RNA, Messenger - genetics Sex differences Toxicology |
| title | Association of polymorphisms in RGS4 and expression of RGS transcripts in the brains of human alcoholics |
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