The AVPR1A gene and substance use disorders: association, replication, and functional evidence.
Biol Psychiatry
; 70(6): 519-27, 2011 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-21514569
ABSTRACT
BACKGROUND:
The liability to addiction has been shown to be highly genetically correlated across drug classes, suggesting nondrug-specific mechanisms.METHODS:
In 757 subjects, we performed association analysis between 1536 single nucleotide polymorphisms (SNPs) in 106 candidate genes and a drug use disorder diagnosis (DUD).RESULTS:
Associations (p ≤ .0008) were detected with three SNPs in the arginine vasopressin 1A receptor gene, AVPR1A, with a gene-wise p value of 3 × 10(-5). Bioinformatic evidence points to a role for rs11174811 (microRNA binding site disruption) in AVPR1A function. Based on literature implicating AVPR1A in social bonding, we tested spousal satisfaction as a mediator of the association of rs11174811 with the DUD. Spousal satisfaction was significantly associated with DUD in males (p < .0001). The functional AVPR1A SNP, rs11174811, was associated with spousal satisfaction in males (p = .007). Spousal satisfaction was a significant mediator of the relationship between rs11174811 and DUD. We also present replication of the association in males between rs11174811 and substance use in one clinically ascertained (n = 1399) and one epidemiologic sample (n = 2231). The direction of the association is consistent across the clinically-ascertained samples but reversed in the epidemiologic sample. Lastly, we found a significant impact of rs11174811 genotype on AVPR1A expression in a postmortem brain sample.CONCLUSIONS:
The findings of this study call for expansion of research into the role of the arginine vasopressin and other neuropeptide system variation in DUD liability.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arginina Vasopressina
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Receptores de Vasopressinas
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Cônjuges
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Transtornos Relacionados ao Uso de Substâncias
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Estudos de Associação Genética
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Apego ao Objeto
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Child
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Female
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Humans
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Male
Idioma:
En
Revista:
Biol Psychiatry
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos