國家衛生研究院 NHRI:Item 3990099045/1441
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    题名: GABA(A) receptor beta isoform protein expression in human alcoholic brain: interaction with genotype
    作者: Buckley, ST;Foley, PF;Innes, DJ;Loh, EW;Shen, Y;Williams, SM;Harper, CG;Tannenberg, AEG;Dodd, PR
    贡献者: Division of Mental Health and Substance Abuse Research
    摘要: Chronic alcohol misuse by human subjects leads to neuronal loss in regions such as the superior frontal cortex. Reduced GABA transmission may mediate this. The expression of GABA(A) receptor beta(1), beta(2) and beta(3) isoform proteins was analyzed by western blotting in vulnerable (superior frontal cortex) and spared (primary motor cortex) cortical tissue obtained at autopsy from Caucasian subjects, and the effect of genotypes of candidate genes for alcoholism assessed. There was a significant regional difference in global isoform expression, but no significant overall group difference in beta(2) or 03 expression between controls and alcoholics undifferentiated by genotype in either cortical region. There were significant, regionally selective, interactions of DRD2B, SLC1A2 and APOE genotypes with P protein expression when alcoholics were compared with controls. In each instance possession of the alcoholism-associated allele increased the beta(2):beta(3) ratio in the pathologically vulnerable region, by two distinct mechanisms. The SFC beta(2):beta(3) ratio in DRD2B-B2,B2 alcoholics was 22% higher than that in DRD2B-B1,B1 alcoholics, and 17% higher than that in DRMB-B2,B2 controls. The SFC beta(2):beta(3) ratio in SLC1A2A603 homozygote alcoholics was 25% higher than that in alcoholics with at least one 603G allele, and 75% higher than that in SLC1A2A603 homozygote controls. The SFC beta(2):beta(3) ratio in alcoholics lacking an APOE epsilon 3 allele was 73% higher than that in alcoholics with at least one epsilon 3 allele, and 70% higher than that in controls without an epsilon 3 allele. ADHI C genotype also differentiated cases and controls, but the effect was not localized. GABRB2 and GRIN2B genotypes were associated with significant regional differences in the pattern of P subunit expression, but this was not influenced by alcoholism status. DRD2A and SLC6A4 genotypes were without significant effect. A restricted set of genotypes may influence subunit expression in this group of high-consumption alcoholics. (c) 2006 Elsevier Ltd. All rights reserved.
    关键词: Biochemistry & Molecular Biology;Neurosciences
    日期: 2006-11
    關聯: Neurochemistry International. 2006 Nov;49(6):557-567.
    Link to: http://dx.doi.org/10.1016/j.neuint.2006.04.008
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0197-0186&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000241633000001
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33749535686
    显示于类别:[羅爾維(2004-2012)] 期刊論文

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