Polymorphisms in the dopamine, serotonin, and norepinephrine transporter genes and their relationships to monoamine metabolite concentrations in CSF of healthy volunteers
Concentrations of monoamine metabolites (MM) in lumbar cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. We investigated the possible relationships between DNA polymorphisms in the dopamine transporter (DAT), serotonin transporter (SERT),...
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| Veröffentlicht in: | Psychiatry research 1998-06, Vol.79 (1), p.1-9 |
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| creator | Jönsson, Erik G Nöthen, Markus M Gustavsson, J.Petter Neidt, Helge Bunzel, Roland Propping, Peter Sedvall, Göran C |
| description | Concentrations of monoamine metabolites (MM) in lumbar cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. We investigated the possible relationships between DNA polymorphisms in the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) genes and CSF concentrations of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (
n=66). The DAT polymorphism was not significantly associated with any of the monoamine metabolites, but a tendency for relationship with 5-HIAA was found in women. For both of the two SERT polymorphisms investigated, a functional promoter polymorphism and an intronic polymorphism without known function, significant relationships were found with CSF MHPG levels. No relationship was found between the SERT polymorphisms and CSF HVA and 5-HIAA. The NET polymorphism was associated with CSF MHPG levels but not with HVA and 5-HIAA concentrations. The results suggest that SERT and NET genotypes may participate differentially in the regulation of the norepinephrine turnover rate under presumed steady-state conditions in the central nervous system. As only limited data so far indicate interactions between the serotonin and norepinephrine systems in the brain, and the NET polymorphism investigated is not known to be of functional significance, the results should be interpreted with caution until replicated. |
| doi_str_mv | 10.1016/S0165-1781(98)00027-4 |
| format | Article |
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n=66). The DAT polymorphism was not significantly associated with any of the monoamine metabolites, but a tendency for relationship with 5-HIAA was found in women. For both of the two SERT polymorphisms investigated, a functional promoter polymorphism and an intronic polymorphism without known function, significant relationships were found with CSF MHPG levels. No relationship was found between the SERT polymorphisms and CSF HVA and 5-HIAA. The NET polymorphism was associated with CSF MHPG levels but not with HVA and 5-HIAA concentrations. The results suggest that SERT and NET genotypes may participate differentially in the regulation of the norepinephrine turnover rate under presumed steady-state conditions in the central nervous system. As only limited data so far indicate interactions between the serotonin and norepinephrine systems in the brain, and the NET polymorphism investigated is not known to be of functional significance, the results should be interpreted with caution until replicated.</description><identifier>ISSN: 0165-1781</identifier><identifier>EISSN: 1872-7123</identifier><identifier>DOI: 10.1016/S0165-1781(98)00027-4</identifier><identifier>PMID: 9676821</identifier><identifier>CODEN: PSRSDR</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>Adult ; Analysis of Variance ; Biogenic Monoamines - cerebrospinal fluid ; Biogenic Monoamines - genetics ; Biogenic Monoamines - metabolism ; Biological and medical sciences ; Brain Chemistry - genetics ; Carrier Proteins - genetics ; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges ; Cerebrospinal fluid ; Cohort Studies ; Dopamine Plasma Membrane Transport Proteins ; Dopamine transporter gene ; Female ; Fundamental and applied biological sciences. Psychology ; Genotype ; Homovanillic Acid - cerebrospinal fluid ; Humans ; Hydroxyindoleacetic Acid - cerebrospinal fluid ; Male ; Membrane Glycoproteins - genetics ; Membrane Transport Proteins ; Methoxyhydroxyphenylglycol - cerebrospinal fluid ; Middle Aged ; Monoamine metabolites (HVA, 5-HIAA, MHPG) ; Nerve Tissue Proteins ; Norepinephrine Plasma Membrane Transport Proteins ; Norepinephrine transporter gene ; Phenotype ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Serotonin Plasma Membrane Transport Proteins ; Serotonin transporter gene ; Sex Factors ; Symporters ; Vertebrates: nervous system and sense organs</subject><ispartof>Psychiatry research, 1998-06, Vol.79 (1), p.1-9</ispartof><rights>1998 Elsevier Science Ireland Ltd</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-2638fb2559ef29214e033fa7b9a64505138ff2e24f127d35dffe4084a70ad7783</citedby><cites>FETCH-LOGICAL-c427t-2638fb2559ef29214e033fa7b9a64505138ff2e24f127d35dffe4084a70ad7783</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0165178198000274$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2343371$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9676821$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:1950055$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Jönsson, Erik G</creatorcontrib><creatorcontrib>Nöthen, Markus M</creatorcontrib><creatorcontrib>Gustavsson, J.Petter</creatorcontrib><creatorcontrib>Neidt, Helge</creatorcontrib><creatorcontrib>Bunzel, Roland</creatorcontrib><creatorcontrib>Propping, Peter</creatorcontrib><creatorcontrib>Sedvall, Göran C</creatorcontrib><title>Polymorphisms in the dopamine, serotonin, and norepinephrine transporter genes and their relationships to monoamine metabolite concentrations in CSF of healthy volunteers</title><title>Psychiatry research</title><addtitle>Psychiatry Res</addtitle><description>Concentrations of monoamine metabolites (MM) in lumbar cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. We investigated the possible relationships between DNA polymorphisms in the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) genes and CSF concentrations of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (
n=66). The DAT polymorphism was not significantly associated with any of the monoamine metabolites, but a tendency for relationship with 5-HIAA was found in women. For both of the two SERT polymorphisms investigated, a functional promoter polymorphism and an intronic polymorphism without known function, significant relationships were found with CSF MHPG levels. No relationship was found between the SERT polymorphisms and CSF HVA and 5-HIAA. The NET polymorphism was associated with CSF MHPG levels but not with HVA and 5-HIAA concentrations. The results suggest that SERT and NET genotypes may participate differentially in the regulation of the norepinephrine turnover rate under presumed steady-state conditions in the central nervous system. As only limited data so far indicate interactions between the serotonin and norepinephrine systems in the brain, and the NET polymorphism investigated is not known to be of functional significance, the results should be interpreted with caution until replicated.</description><subject>Adult</subject><subject>Analysis of Variance</subject><subject>Biogenic Monoamines - cerebrospinal fluid</subject><subject>Biogenic Monoamines - genetics</subject><subject>Biogenic Monoamines - metabolism</subject><subject>Biological and medical sciences</subject><subject>Brain Chemistry - genetics</subject><subject>Carrier Proteins - genetics</subject><subject>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</subject><subject>Cerebrospinal fluid</subject><subject>Cohort Studies</subject><subject>Dopamine Plasma Membrane Transport Proteins</subject><subject>Dopamine transporter gene</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genotype</subject><subject>Homovanillic Acid - cerebrospinal fluid</subject><subject>Humans</subject><subject>Hydroxyindoleacetic Acid - cerebrospinal fluid</subject><subject>Male</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Transport Proteins</subject><subject>Methoxyhydroxyphenylglycol - cerebrospinal fluid</subject><subject>Middle Aged</subject><subject>Monoamine metabolites (HVA, 5-HIAA, MHPG)</subject><subject>Nerve Tissue Proteins</subject><subject>Norepinephrine Plasma Membrane Transport Proteins</subject><subject>Norepinephrine transporter gene</subject><subject>Phenotype</subject><subject>Polymerase Chain Reaction</subject><subject>Polymorphism, Genetic</subject><subject>Serotonin Plasma Membrane Transport Proteins</subject><subject>Serotonin transporter gene</subject><subject>Sex Factors</subject><subject>Symporters</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0165-1781</issn><issn>1872-7123</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkdGK1DAUhoMo6-zoIyzkQsSFrTZJ26RXiwyuCgsKq9chbU9stE1qkq7MK_mUpp0yt96chPN_-U84P0JXJH9LclK9e0ilzAgX5E0trvM8pzwrnqAdEZxmnFD2FO3OyHN0GcLPBSJ1fYEu6opXgpId-vvVDcfR-ak3YQzYWBx7wJ2b1Ggs3OAA3kVnjb3BynbYOg9TEqbep4qjVzZMzkfw-AdYCCuUHIzHHgYVjbOhN1PA0eHRWbe64hGiatxgIuDW2RZs8lnRZf7h4Q47jXtQQ-yP-NENs40APrxAz7QaArzczj36fvfh2-FTdv_l4-fD-_usLSiPGa2Y0A0tyxo0rSkpIGdMK97UqirKvCRJ1hRooQnlHSs7raHIRaF4rjrOBduj7OQb_sA0N3LyZlT-KJ0ycmv9SjeQBSsoY4l_feIn737PEKIcTWhhGJQFNwcp0taFqBfj8gS23oXgQZ-tSS6XTOWaqVwCk7WQa6Zpyh5dbQPmZoTu_GoLMemvNl2FVg06hdKacMYoKxjjC3Z7wiAt79GAl6E1kNbfGQ9tlJ0z__nIP8g3wtk</recordid><startdate>19980602</startdate><enddate>19980602</enddate><creator>Jönsson, Erik G</creator><creator>Nöthen, Markus M</creator><creator>Gustavsson, J.Petter</creator><creator>Neidt, Helge</creator><creator>Bunzel, Roland</creator><creator>Propping, Peter</creator><creator>Sedvall, Göran C</creator><general>Elsevier Ireland Ltd</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>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>19980602</creationdate><title>Polymorphisms in the dopamine, serotonin, and norepinephrine transporter genes and their relationships to monoamine metabolite concentrations in CSF of healthy volunteers</title><author>Jönsson, Erik G ; Nöthen, Markus M ; Gustavsson, J.Petter ; Neidt, Helge ; Bunzel, Roland ; Propping, Peter ; Sedvall, Göran C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-2638fb2559ef29214e033fa7b9a64505138ff2e24f127d35dffe4084a70ad7783</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1998</creationdate><topic>Adult</topic><topic>Analysis of Variance</topic><topic>Biogenic Monoamines - cerebrospinal fluid</topic><topic>Biogenic Monoamines - genetics</topic><topic>Biogenic Monoamines - metabolism</topic><topic>Biological and medical sciences</topic><topic>Brain Chemistry - genetics</topic><topic>Carrier Proteins - genetics</topic><topic>Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges</topic><topic>Cerebrospinal fluid</topic><topic>Cohort Studies</topic><topic>Dopamine Plasma Membrane Transport Proteins</topic><topic>Dopamine transporter gene</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genotype</topic><topic>Homovanillic Acid - cerebrospinal fluid</topic><topic>Humans</topic><topic>Hydroxyindoleacetic Acid - cerebrospinal fluid</topic><topic>Male</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Transport Proteins</topic><topic>Methoxyhydroxyphenylglycol - cerebrospinal fluid</topic><topic>Middle Aged</topic><topic>Monoamine metabolites (HVA, 5-HIAA, MHPG)</topic><topic>Nerve Tissue Proteins</topic><topic>Norepinephrine Plasma Membrane Transport Proteins</topic><topic>Norepinephrine transporter gene</topic><topic>Phenotype</topic><topic>Polymerase Chain Reaction</topic><topic>Polymorphism, Genetic</topic><topic>Serotonin Plasma Membrane Transport Proteins</topic><topic>Serotonin transporter gene</topic><topic>Sex Factors</topic><topic>Symporters</topic><topic>Vertebrates: nervous system and sense organs</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jönsson, Erik G</creatorcontrib><creatorcontrib>Nöthen, Markus M</creatorcontrib><creatorcontrib>Gustavsson, J.Petter</creatorcontrib><creatorcontrib>Neidt, Helge</creatorcontrib><creatorcontrib>Bunzel, Roland</creatorcontrib><creatorcontrib>Propping, Peter</creatorcontrib><creatorcontrib>Sedvall, Göran C</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>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Psychiatry research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jönsson, Erik G</au><au>Nöthen, Markus M</au><au>Gustavsson, J.Petter</au><au>Neidt, Helge</au><au>Bunzel, Roland</au><au>Propping, Peter</au><au>Sedvall, Göran C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Polymorphisms in the dopamine, serotonin, and norepinephrine transporter genes and their relationships to monoamine metabolite concentrations in CSF of healthy volunteers</atitle><jtitle>Psychiatry research</jtitle><addtitle>Psychiatry Res</addtitle><date>1998-06-02</date><risdate>1998</risdate><volume>79</volume><issue>1</issue><spage>1</spage><epage>9</epage><pages>1-9</pages><issn>0165-1781</issn><eissn>1872-7123</eissn><coden>PSRSDR</coden><abstract>Concentrations of monoamine metabolites (MM) in lumbar cerebrospinal fluid (CSF) have been used extensively as indirect estimates of monoamine turnover in the brain. We investigated the possible relationships between DNA polymorphisms in the dopamine transporter (DAT), serotonin transporter (SERT), and norepinephrine transporter (NET) genes and CSF concentrations of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) in healthy volunteers (
n=66). The DAT polymorphism was not significantly associated with any of the monoamine metabolites, but a tendency for relationship with 5-HIAA was found in women. For both of the two SERT polymorphisms investigated, a functional promoter polymorphism and an intronic polymorphism without known function, significant relationships were found with CSF MHPG levels. No relationship was found between the SERT polymorphisms and CSF HVA and 5-HIAA. The NET polymorphism was associated with CSF MHPG levels but not with HVA and 5-HIAA concentrations. The results suggest that SERT and NET genotypes may participate differentially in the regulation of the norepinephrine turnover rate under presumed steady-state conditions in the central nervous system. As only limited data so far indicate interactions between the serotonin and norepinephrine systems in the brain, and the NET polymorphism investigated is not known to be of functional significance, the results should be interpreted with caution until replicated.</abstract><cop>Shannon</cop><pub>Elsevier Ireland Ltd</pub><pmid>9676821</pmid><doi>10.1016/S0165-1781(98)00027-4</doi><tpages>9</tpages></addata></record> |
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| ispartof | Psychiatry research, 1998-06, Vol.79 (1), p.1-9 |
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| subjects | Adult Analysis of Variance Biogenic Monoamines - cerebrospinal fluid Biogenic Monoamines - genetics Biogenic Monoamines - metabolism Biological and medical sciences Brain Chemistry - genetics Carrier Proteins - genetics Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges Cerebrospinal fluid Cohort Studies Dopamine Plasma Membrane Transport Proteins Dopamine transporter gene Female Fundamental and applied biological sciences. Psychology Genotype Homovanillic Acid - cerebrospinal fluid Humans Hydroxyindoleacetic Acid - cerebrospinal fluid Male Membrane Glycoproteins - genetics Membrane Transport Proteins Methoxyhydroxyphenylglycol - cerebrospinal fluid Middle Aged Monoamine metabolites (HVA, 5-HIAA, MHPG) Nerve Tissue Proteins Norepinephrine Plasma Membrane Transport Proteins Norepinephrine transporter gene Phenotype Polymerase Chain Reaction Polymorphism, Genetic Serotonin Plasma Membrane Transport Proteins Serotonin transporter gene Sex Factors Symporters Vertebrates: nervous system and sense organs |
| title | Polymorphisms in the dopamine, serotonin, and norepinephrine transporter genes and their relationships to monoamine metabolite concentrations in CSF of healthy volunteers |
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