Genotype Influences In Vivo Dopamine Transporter Availability in Human Striatum
In vivo availability of striatal dopamine transporter (DAT) protein has been reported to be reduced among alcoholics, and allelic variation of the DAT gene (SLC6A3) has been associated with severity of alcohol withdrawal. We examined the VNTR polymorphism of the 3′ untranslated region of SLC6A3 and...
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| creator | Heinz, Andreas Goldman, David Jones, Douglas W Palmour, Roberta Hommer, Dan Gorey, Julia G Lee, Kan S Linnoila, Markku Weinberger, Daniel R |
| description | In vivo availability of striatal dopamine transporter (DAT) protein has been reported to be reduced among alcoholics, and allelic variation of the DAT gene (SLC6A3) has been associated with severity of alcohol withdrawal. We examined the VNTR polymorphism of the 3′ untranslated region of SLC6A3 and DAT protein availability in 14 abstinent alcoholics and 11 control subjects. Single photon emission computed tomography (SPECT) and plasma levels of the radioligand [I-123]β-CIT were used to quantify DAT protein availability. Individuals with the 9-repeat/10-repeat genotype had a mean 22% reduction of DAT protein availability in putamen compared with 10-repeat homozygous individuals (t = 2.14, df = 23, p < .05). Consistent with earlier studies, alcoholism, per se, was not significantly associated with either DAT availability or DAT genotype. These findings suggest that the VNTR polymorphism of the DAT gene effects translation of the DAT protein. This effect may explain a variety of clinical associations that have been reported with this polymorphism. |
| doi_str_mv | 10.1016/S0893-133X(99)00099-8 |
| format | Article |
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We examined the VNTR polymorphism of the 3′ untranslated region of SLC6A3 and DAT protein availability in 14 abstinent alcoholics and 11 control subjects. Single photon emission computed tomography (SPECT) and plasma levels of the radioligand [I-123]β-CIT were used to quantify DAT protein availability. Individuals with the 9-repeat/10-repeat genotype had a mean 22% reduction of DAT protein availability in putamen compared with 10-repeat homozygous individuals (t = 2.14, df = 23, p < .05). Consistent with earlier studies, alcoholism, per se, was not significantly associated with either DAT availability or DAT genotype. These findings suggest that the VNTR polymorphism of the DAT gene effects translation of the DAT protein. This effect may explain a variety of clinical associations that have been reported with this polymorphism.</description><identifier>ISSN: 0893-133X</identifier><identifier>EISSN: 1740-634X</identifier><identifier>DOI: 10.1016/S0893-133X(99)00099-8</identifier><identifier>PMID: 10649826</identifier><identifier>CODEN: NEROEW</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>3' Untranslated Regions - genetics ; Adult ; Alcohol use ; Alcohol withdrawal ; Alcoholism ; Alcoholism - genetics ; Alcoholism - metabolism ; Alcoholism and acute alcohol poisoning ; Attention deficit hyperactivity disorder ; Biological and medical sciences ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cell physiology ; Cocaine - analogs & derivatives ; Cocaine - pharmacokinetics ; Corpus Striatum - diagnostic imaging ; Corpus Striatum - metabolism ; Dopamine ; Dopamine Plasma Membrane Transport Proteins ; Dopamine transporter ; Drug withdrawal ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Genotype ; Genotype & phenotype ; Homozygote ; Humans ; Iodine Radioisotopes - pharmacokinetics ; Medical sciences ; Membrane Glycoproteins ; Membrane Transport Proteins ; Minisatellite Repeats ; Molecular and cellular biology ; Nerve Tissue Proteins ; Neurotransmission ; Polymorphism ; Polymorphism, Genetic ; Proteins ; Reference Values ; SLC6A3 ; SPECT ; Temperance ; Tomography ; Tomography, Emission-Computed, Single-Photon ; Toxicology ; β-CIT</subject><ispartof>Neuropsychopharmacology (New York, N.Y.), 2000-02, Vol.22 (2), p.133-139</ispartof><rights>2000 American College of Neuropsychopharmacology</rights><rights>2000 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Feb 2000</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c548t-d8feccefd5f63353fea424db141fb7d18ac5e161de3947f23fd870d84765c2f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1236810$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10649826$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Heinz, Andreas</creatorcontrib><creatorcontrib>Goldman, David</creatorcontrib><creatorcontrib>Jones, Douglas W</creatorcontrib><creatorcontrib>Palmour, Roberta</creatorcontrib><creatorcontrib>Hommer, Dan</creatorcontrib><creatorcontrib>Gorey, Julia G</creatorcontrib><creatorcontrib>Lee, Kan S</creatorcontrib><creatorcontrib>Linnoila, Markku</creatorcontrib><creatorcontrib>Weinberger, Daniel R</creatorcontrib><title>Genotype Influences In Vivo Dopamine Transporter Availability in Human Striatum</title><title>Neuropsychopharmacology (New York, N.Y.)</title><addtitle>Neuropsychopharmacology</addtitle><description>In vivo availability of striatal dopamine transporter (DAT) protein has been reported to be reduced among alcoholics, and allelic variation of the DAT gene (SLC6A3) has been associated with severity of alcohol withdrawal. We examined the VNTR polymorphism of the 3′ untranslated region of SLC6A3 and DAT protein availability in 14 abstinent alcoholics and 11 control subjects. Single photon emission computed tomography (SPECT) and plasma levels of the radioligand [I-123]β-CIT were used to quantify DAT protein availability. Individuals with the 9-repeat/10-repeat genotype had a mean 22% reduction of DAT protein availability in putamen compared with 10-repeat homozygous individuals (t = 2.14, df = 23, p < .05). Consistent with earlier studies, alcoholism, per se, was not significantly associated with either DAT availability or DAT genotype. These findings suggest that the VNTR polymorphism of the DAT gene effects translation of the DAT protein. This effect may explain a variety of clinical associations that have been reported with this polymorphism.</description><subject>3' Untranslated Regions - genetics</subject><subject>Adult</subject><subject>Alcohol use</subject><subject>Alcohol withdrawal</subject><subject>Alcoholism</subject><subject>Alcoholism - genetics</subject><subject>Alcoholism - metabolism</subject><subject>Alcoholism and acute alcohol poisoning</subject><subject>Attention deficit hyperactivity disorder</subject><subject>Biological and medical sciences</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cell physiology</subject><subject>Cocaine - analogs & derivatives</subject><subject>Cocaine - pharmacokinetics</subject><subject>Corpus Striatum - diagnostic imaging</subject><subject>Corpus Striatum - metabolism</subject><subject>Dopamine</subject><subject>Dopamine Plasma Membrane Transport Proteins</subject><subject>Dopamine transporter</subject><subject>Drug withdrawal</subject><subject>Fundamental and applied biological sciences. 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We examined the VNTR polymorphism of the 3′ untranslated region of SLC6A3 and DAT protein availability in 14 abstinent alcoholics and 11 control subjects. Single photon emission computed tomography (SPECT) and plasma levels of the radioligand [I-123]β-CIT were used to quantify DAT protein availability. Individuals with the 9-repeat/10-repeat genotype had a mean 22% reduction of DAT protein availability in putamen compared with 10-repeat homozygous individuals (t = 2.14, df = 23, p < .05). Consistent with earlier studies, alcoholism, per se, was not significantly associated with either DAT availability or DAT genotype. These findings suggest that the VNTR polymorphism of the DAT gene effects translation of the DAT protein. This effect may explain a variety of clinical associations that have been reported with this polymorphism.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>10649826</pmid><doi>10.1016/S0893-133X(99)00099-8</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 3' Untranslated Regions - genetics Adult Alcohol use Alcohol withdrawal Alcoholism Alcoholism - genetics Alcoholism - metabolism Alcoholism and acute alcohol poisoning Attention deficit hyperactivity disorder Biological and medical sciences Carrier Proteins - genetics Carrier Proteins - metabolism Cell physiology Cocaine - analogs & derivatives Cocaine - pharmacokinetics Corpus Striatum - diagnostic imaging Corpus Striatum - metabolism Dopamine Dopamine Plasma Membrane Transport Proteins Dopamine transporter Drug withdrawal Fundamental and applied biological sciences. Psychology Gene expression Genotype Genotype & phenotype Homozygote Humans Iodine Radioisotopes - pharmacokinetics Medical sciences Membrane Glycoproteins Membrane Transport Proteins Minisatellite Repeats Molecular and cellular biology Nerve Tissue Proteins Neurotransmission Polymorphism Polymorphism, Genetic Proteins Reference Values SLC6A3 SPECT Temperance Tomography Tomography, Emission-Computed, Single-Photon Toxicology β-CIT |
| title | Genotype Influences In Vivo Dopamine Transporter Availability in Human Striatum |
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