Source:http://linkedlifedata.com/resource/pubmed/id/15274050
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2004-7-26
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pubmed:abstractText |
Alcohol dependence is a highly prevalent disorder that is associated with serious morbidity and mortality. Because the GABAA neurotransmitter receptor is an important mediator for several behavioral effects of alcohol, genes encoding GABA-related proteins are functional candidates to influence risk of alcohol dependence. Two genome-wide scans showed linkage of alcohol dependence to a region on chromosome 4p, which contains a cluster of genes encoding GABAA receptor subunits. A recent effort to fine map that region showed a haplotypic association of alcohol dependence to the gene encoding the GABAA receptor alpha-2 subunit (GABRA2). We examined 10 single nucleotide polymorphisms (SNPs) spanning the coding region of this gene in samples of European American subjects with alcohol dependence (n = 446), and controls (n = 334) screened to exclude substance use disorders. There was evidence of association to alcohol dependence for seven adjacent markers spanning 98,000 bp in the middle and 3'-portion of the GABRA2 gene (range of P-values = 0.008-0.03). When the subset of the alcohol-dependent subjects excluding those with a diagnosis of cocaine or opioid dependence or major depressive episode (n = 198) was examined, the strength of the association was increased across these 7 SNPs (range of P-values = 0.002-0.007). Two common haplotypes in this region accounted for 90.8% of chromosomes. The more common haplotype was present in 55.6% of control group chromosomes versus 48.2% of alcohol-dependent subjects (P = 0.007) and 45.8% of subjects with alcohol dependence but no co-morbid drug dependence or depression (P = 0.003). These findings replicate and extend recently reported findings, which together underscore the potential contribution of polymorphic variation at the GABRA2 locus to the risk for alcohol dependence.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/K24-AA13736,
http://linkedlifedata.com/resource/pubmed/grant/K24-DA15105,
http://linkedlifedata.com/resource/pubmed/grant/M01-RR06192,
http://linkedlifedata.com/resource/pubmed/grant/P50-AA03510,
http://linkedlifedata.com/resource/pubmed/grant/R01-AA11330
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1552-4841
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2004 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
129B
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
104-9
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pubmed:dateRevised |
2008-5-21
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pubmed:meshHeading |
pubmed-meshheading:15274050-Adult,
pubmed-meshheading:15274050-Alcoholism,
pubmed-meshheading:15274050-Alleles,
pubmed-meshheading:15274050-Chromosomes, Human, Pair 4,
pubmed-meshheading:15274050-DNA,
pubmed-meshheading:15274050-DNA Mutational Analysis,
pubmed-meshheading:15274050-Female,
pubmed-meshheading:15274050-Gene Frequency,
pubmed-meshheading:15274050-Genotype,
pubmed-meshheading:15274050-Haplotypes,
pubmed-meshheading:15274050-Humans,
pubmed-meshheading:15274050-Male,
pubmed-meshheading:15274050-Middle Aged,
pubmed-meshheading:15274050-Multigene Family,
pubmed-meshheading:15274050-Polymorphism, Single Nucleotide,
pubmed-meshheading:15274050-Protein Subunits,
pubmed-meshheading:15274050-Receptors, GABA-A
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pubmed:year |
2004
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pubmed:articleTitle |
Allelic and haplotypic association of GABRA2 with alcohol dependence.
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pubmed:affiliation |
Department of Psychiatry, Alcohol Research Center, University of Connecticut School of Medicine, Farmington, Connecticut 06030-2103, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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