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Association analysis of GABRB3 promoter variants with heroin dependence.
Chen, Chia-Hsiang; Huang, Chia-Chun; Liao, Ding-Lieh.
Afiliación
  • Chen CH; Department of Psychiatry, Chang Gung Memorial Hospital-Linkou, Taoyuan, Taiwan; Department and Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan.
  • Huang CC; Institute of Medical Sciences, Tzu-Chi University, Hualien, Taiwan.
  • Liao DL; Bali Psychiatric Center, Department of Health, Executive Yuan, Taipei, Taiwan.
PLoS One ; 9(7): e102227, 2014.
Article en En | MEDLINE | ID: mdl-25025424
GABRB3 encoding the ß3 subunit of GABAA receptor has been implicated in multiple neuropsychiatric disorders, including substance abuse. Previous studies reported that SNPs at the 5' regulatory region of GABRB3 could regulate GABRB3 gene expression and associated with childhood absence epilepsy (CAE). The study aimed to investigate whether SNPs at the 5' regulatory region of GABRB3 were associated with heroin dependence in our population. We first re-sequenced 1.5 kb of the 5'regulatory region of GABRB3 gene to examine the SNP profile in the genomic DNA of 365 control subjects. Then, we conducted a case-control association analysis between 576 subjects with heroin dependence (549 males, 27 females) and 886 controls (472 males, 414 females) by genotyping the rs4906902 as a tag SNP. We also conducted a reporter gene assay to assess the promoter activity of two major haplotypes derived from SNPs at this region. We detected 3 common SNPs (rs4906902, rs8179184 and rs20317) at this region that had strong pair-wise linkage disequilibrium. The C allele of rs4906902 was found to be associated with increased risk of heroin dependence (odds ratio:1.27, p = 0.002). Two major haplotypes (C-A-G and T-G-C) derived from these 3 SNPs accounted for 99% of this sample, and reporter gene activity assay showed that haplotype C-A-G that contained the C allele of the tag SNP rs4906902 had higher activity than haplotype T-G-C. Our data suggest that GABRB3 might be associated with heroin dependence, and increased expression of GABRB3 might contribute to the pathogenesis of heroin dependence.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regiones Promotoras Genéticas / Receptores de GABA-A / Dependencia de Heroína Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2014 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regiones Promotoras Genéticas / Receptores de GABA-A / Dependencia de Heroína Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2014 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos