Serotonin-related gene polymorphisms and central nervous system serotonin function
Central nervous system (CNS) serotonergic function affects a wide range of biological and behavioral functions affecting health and disease. Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and mon...
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| Veröffentlicht in: | Neuropsychopharmacology (New York, N.Y.) N.Y.), 2003-03, Vol.28 (3), p.533-541 |
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| creator | WILLIAMS, Redford B MARCHUK, Douglas A SUAREZ, Edward C CLARY, Greg L SVENSON, Ingrid K SIEGLER, Ilene C GADDE, Kishore M BAREFOOT, John C GRICHNIK, Katherine HELMS, Michael J KUHN, Cynthia M LEWIS, James G SCHANBERG, Saul M STAFFORD-SMITH, Mark |
| description | Central nervous system (CNS) serotonergic function affects a wide range of biological and behavioral functions affecting health and disease. Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and monoamine oxidase A (MAOA-uVNTR) are associated with CNS serotonin turnover-indexed by cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA)-in a community sample of healthy adults. Subjects were 165 community volunteers without current medical or psychiatric illness, stratified with respect to ethnicity, gender, and socioeconomic status who underwent inpatient evaluation in the General Clinical Research Center of a university medical center. A significant ethnicity x genotype interaction (P=0.008) indicated that, compared to the long/long and long/short genotypes, the 5HTTLPR short/short genotype was associated with higher CSF 5-HIAA levels in African Americans, but with lower levels in Caucasians. A gender x genotype interaction (P=0.04) indicated that 5HTTLPR short/short genotype was associated with higher 5-HIAA levels in women but with lower levels in men. MAOA-uVNTR 3.5 and 4 repeat alleles were associated with higher 5-HIAA (P=0.03) levels in men, but were unrelated to 5-HIAA levels in women. These findings suggest that effects of serotonin-related gene polymorphisms on CNS serotonergic function vary as a function of both ethnicity and gender. Further research will be required to determine the mechanism(s) underlying these differential effects. In the meanwhile, both ethnicity and gender should be taken into account in research evaluating effects of these and related polymorphisms on CNS serotonergic function, as well as the broad range of biological and behavioral functions that are regulated by CNS serotonergic function. |
| doi_str_mv | 10.1038/sj.npp.1300054 |
| format | Article |
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Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and monoamine oxidase A (MAOA-uVNTR) are associated with CNS serotonin turnover-indexed by cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA)-in a community sample of healthy adults. Subjects were 165 community volunteers without current medical or psychiatric illness, stratified with respect to ethnicity, gender, and socioeconomic status who underwent inpatient evaluation in the General Clinical Research Center of a university medical center. A significant ethnicity x genotype interaction (P=0.008) indicated that, compared to the long/long and long/short genotypes, the 5HTTLPR short/short genotype was associated with higher CSF 5-HIAA levels in African Americans, but with lower levels in Caucasians. A gender x genotype interaction (P=0.04) indicated that 5HTTLPR short/short genotype was associated with higher 5-HIAA levels in women but with lower levels in men. MAOA-uVNTR 3.5 and 4 repeat alleles were associated with higher 5-HIAA (P=0.03) levels in men, but were unrelated to 5-HIAA levels in women. These findings suggest that effects of serotonin-related gene polymorphisms on CNS serotonergic function vary as a function of both ethnicity and gender. Further research will be required to determine the mechanism(s) underlying these differential effects. In the meanwhile, both ethnicity and gender should be taken into account in research evaluating effects of these and related polymorphisms on CNS serotonergic function, as well as the broad range of biological and behavioral functions that are regulated by CNS serotonergic function.</description><identifier>ISSN: 0893-133X</identifier><identifier>EISSN: 1740-634X</identifier><identifier>DOI: 10.1038/sj.npp.1300054</identifier><identifier>PMID: 12629534</identifier><identifier>CODEN: NEROEW</identifier><language>eng</language><publisher>New York, NY: Nature Publishing</publisher><subject>Adult ; Analysis of Variance ; Behavioral sciences ; Biological and medical sciences ; Carrier Proteins - genetics ; Central nervous system ; Central Nervous System - metabolism ; Central neurotransmission. Neuromudulation. Pathways and receptors ; Ethnic Groups - psychology ; Ethnic Groups - statistics & numerical data ; Ethnicity ; Female ; Fundamental and applied biological sciences. Psychology ; Gender ; Genes ; Genotype ; Genotype & phenotype ; Humans ; Hydroxyindoleacetic Acid - cerebrospinal fluid ; Male ; Membrane Glycoproteins - genetics ; Membrane Transport Proteins ; Middle Aged ; Monoamine Oxidase - genetics ; Nerve Tissue Proteins ; Nervous system ; Polymorphism, Genetic - genetics ; Proteins ; Serotonin ; Serotonin - genetics ; Serotonin - metabolism ; Serotonin Plasma Membrane Transport Proteins ; Sex Factors ; Socioeconomic Factors ; Vertebrates: nervous system and sense organs</subject><ispartof>Neuropsychopharmacology (New York, N.Y.), 2003-03, Vol.28 (3), p.533-541</ispartof><rights>2003 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Mar 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-c86bc5595305ad270a628608e63eef7f60849317e73b7daf036b836fa5f9a1ea3</citedby><cites>FETCH-LOGICAL-c454t-c86bc5595305ad270a628608e63eef7f60849317e73b7daf036b836fa5f9a1ea3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14775583$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12629534$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>WILLIAMS, Redford B</creatorcontrib><creatorcontrib>MARCHUK, Douglas A</creatorcontrib><creatorcontrib>SUAREZ, Edward C</creatorcontrib><creatorcontrib>CLARY, Greg L</creatorcontrib><creatorcontrib>SVENSON, Ingrid K</creatorcontrib><creatorcontrib>SIEGLER, Ilene C</creatorcontrib><creatorcontrib>GADDE, Kishore M</creatorcontrib><creatorcontrib>BAREFOOT, John C</creatorcontrib><creatorcontrib>GRICHNIK, Katherine</creatorcontrib><creatorcontrib>HELMS, Michael J</creatorcontrib><creatorcontrib>KUHN, Cynthia M</creatorcontrib><creatorcontrib>LEWIS, James G</creatorcontrib><creatorcontrib>SCHANBERG, Saul M</creatorcontrib><creatorcontrib>STAFFORD-SMITH, Mark</creatorcontrib><title>Serotonin-related gene polymorphisms and central nervous system serotonin function</title><title>Neuropsychopharmacology (New York, N.Y.)</title><addtitle>Neuropsychopharmacology</addtitle><description>Central nervous system (CNS) serotonergic function affects a wide range of biological and behavioral functions affecting health and disease. Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and monoamine oxidase A (MAOA-uVNTR) are associated with CNS serotonin turnover-indexed by cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA)-in a community sample of healthy adults. Subjects were 165 community volunteers without current medical or psychiatric illness, stratified with respect to ethnicity, gender, and socioeconomic status who underwent inpatient evaluation in the General Clinical Research Center of a university medical center. A significant ethnicity x genotype interaction (P=0.008) indicated that, compared to the long/long and long/short genotypes, the 5HTTLPR short/short genotype was associated with higher CSF 5-HIAA levels in African Americans, but with lower levels in Caucasians. A gender x genotype interaction (P=0.04) indicated that 5HTTLPR short/short genotype was associated with higher 5-HIAA levels in women but with lower levels in men. MAOA-uVNTR 3.5 and 4 repeat alleles were associated with higher 5-HIAA (P=0.03) levels in men, but were unrelated to 5-HIAA levels in women. These findings suggest that effects of serotonin-related gene polymorphisms on CNS serotonergic function vary as a function of both ethnicity and gender. Further research will be required to determine the mechanism(s) underlying these differential effects. In the meanwhile, both ethnicity and gender should be taken into account in research evaluating effects of these and related polymorphisms on CNS serotonergic function, as well as the broad range of biological and behavioral functions that are regulated by CNS serotonergic function.</description><subject>Adult</subject><subject>Analysis of Variance</subject><subject>Behavioral sciences</subject><subject>Biological and medical sciences</subject><subject>Carrier Proteins - genetics</subject><subject>Central nervous system</subject><subject>Central Nervous System - metabolism</subject><subject>Central neurotransmission. Neuromudulation. Pathways and receptors</subject><subject>Ethnic Groups - psychology</subject><subject>Ethnic Groups - statistics & numerical data</subject><subject>Ethnicity</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gender</subject><subject>Genes</subject><subject>Genotype</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Hydroxyindoleacetic Acid - cerebrospinal fluid</subject><subject>Male</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Transport Proteins</subject><subject>Middle Aged</subject><subject>Monoamine Oxidase - genetics</subject><subject>Nerve Tissue Proteins</subject><subject>Nervous system</subject><subject>Polymorphism, Genetic - genetics</subject><subject>Proteins</subject><subject>Serotonin</subject><subject>Serotonin - genetics</subject><subject>Serotonin - metabolism</subject><subject>Serotonin Plasma Membrane Transport Proteins</subject><subject>Sex Factors</subject><subject>Socioeconomic Factors</subject><subject>Vertebrates: nervous system and sense organs</subject><issn>0893-133X</issn><issn>1740-634X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkE2L1TAUhoMozp2PrUspgrPrNenJR7uUwRmFAcEPmF3ITU-0lzapOa1w_72RqQy4OmfxvC8vD2OvBN8LDu07Ou7jPO8FcM6VfMZ2wkhea5APz9mOtx3UAuDhjJ0THTkXyuj2JTsTjW46BXLHvnzFnJYUh1hnHN2CffUDI1ZzGk9TyvPPgSaqXOwrj3HJbqwi5t9ppYpOtOBU0b98FdbolyHFS_YiuJHwarsX7Pvth283H-v7z3efbt7f114qudS-1QevVJnBlesbw51uWs1b1IAYTCiv7EAYNHAwvQsc9KEFHZwKnRPo4IJdP_bOOf1akRY7DeRxHF3EMtAa4B2U8gK--Q88pjXHss02jWpkIxQv0P4R8jkRZQx2zsPk8skKbv-qtnS0RbXdVJfA6611PUzYP-Gb2wK83QBH3o0hu-gHeuKkMUq1AH8A_h-Iug</recordid><startdate>20030301</startdate><enddate>20030301</enddate><creator>WILLIAMS, Redford B</creator><creator>MARCHUK, Douglas A</creator><creator>SUAREZ, Edward C</creator><creator>CLARY, Greg L</creator><creator>SVENSON, Ingrid K</creator><creator>SIEGLER, Ilene C</creator><creator>GADDE, Kishore M</creator><creator>BAREFOOT, John C</creator><creator>GRICHNIK, Katherine</creator><creator>HELMS, Michael J</creator><creator>KUHN, Cynthia M</creator><creator>LEWIS, James G</creator><creator>SCHANBERG, Saul M</creator><creator>STAFFORD-SMITH, Mark</creator><general>Nature Publishing</general><general>Nature Publishing Group</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>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20030301</creationdate><title>Serotonin-related gene polymorphisms and central nervous system serotonin function</title><author>WILLIAMS, Redford B ; MARCHUK, Douglas A ; SUAREZ, Edward C ; CLARY, Greg L ; SVENSON, Ingrid K ; SIEGLER, Ilene C ; GADDE, Kishore M ; BAREFOOT, John C ; GRICHNIK, Katherine ; HELMS, Michael J ; KUHN, Cynthia M ; LEWIS, James G ; SCHANBERG, Saul M ; STAFFORD-SMITH, Mark</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-c86bc5595305ad270a628608e63eef7f60849317e73b7daf036b836fa5f9a1ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adult</topic><topic>Analysis of Variance</topic><topic>Behavioral sciences</topic><topic>Biological and medical sciences</topic><topic>Carrier Proteins - genetics</topic><topic>Central nervous system</topic><topic>Central Nervous System - metabolism</topic><topic>Central neurotransmission. 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Our objective in this study was to determine whether functional polymorphisms of the genes that encode for the serotonin transporter promoter (5HTTLPR) and monoamine oxidase A (MAOA-uVNTR) are associated with CNS serotonin turnover-indexed by cerebrospinal fluid levels of 5-hydroxyindoleacetic acid (5-HIAA)-in a community sample of healthy adults. Subjects were 165 community volunteers without current medical or psychiatric illness, stratified with respect to ethnicity, gender, and socioeconomic status who underwent inpatient evaluation in the General Clinical Research Center of a university medical center. A significant ethnicity x genotype interaction (P=0.008) indicated that, compared to the long/long and long/short genotypes, the 5HTTLPR short/short genotype was associated with higher CSF 5-HIAA levels in African Americans, but with lower levels in Caucasians. A gender x genotype interaction (P=0.04) indicated that 5HTTLPR short/short genotype was associated with higher 5-HIAA levels in women but with lower levels in men. MAOA-uVNTR 3.5 and 4 repeat alleles were associated with higher 5-HIAA (P=0.03) levels in men, but were unrelated to 5-HIAA levels in women. These findings suggest that effects of serotonin-related gene polymorphisms on CNS serotonergic function vary as a function of both ethnicity and gender. Further research will be required to determine the mechanism(s) underlying these differential effects. In the meanwhile, both ethnicity and gender should be taken into account in research evaluating effects of these and related polymorphisms on CNS serotonergic function, as well as the broad range of biological and behavioral functions that are regulated by CNS serotonergic function.</abstract><cop>New York, NY</cop><pub>Nature Publishing</pub><pmid>12629534</pmid><doi>10.1038/sj.npp.1300054</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Analysis of Variance Behavioral sciences Biological and medical sciences Carrier Proteins - genetics Central nervous system Central Nervous System - metabolism Central neurotransmission. Neuromudulation. Pathways and receptors Ethnic Groups - psychology Ethnic Groups - statistics & numerical data Ethnicity Female Fundamental and applied biological sciences. Psychology Gender Genes Genotype Genotype & phenotype Humans Hydroxyindoleacetic Acid - cerebrospinal fluid Male Membrane Glycoproteins - genetics Membrane Transport Proteins Middle Aged Monoamine Oxidase - genetics Nerve Tissue Proteins Nervous system Polymorphism, Genetic - genetics Proteins Serotonin Serotonin - genetics Serotonin - metabolism Serotonin Plasma Membrane Transport Proteins Sex Factors Socioeconomic Factors Vertebrates: nervous system and sense organs |
| title | Serotonin-related gene polymorphisms and central nervous system serotonin function |
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