Association of the histidine-triad nucleotide-binding protein-1 (HINT1) gene variants with nicotine dependence

被引:21
作者
Jackson, K. J.
Chen, Q.
Chen, J.
Aggen, S. H.
Kendler, K. S.
Chen, X. [1 ]
机构
[1] Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
关键词
histidine triad nucleotide-binding protein-1 (HINT1); single-nucleotide polymorphism; ND; FTND; nucleus accumbens; protein expression; INTERACTIVE PROTEIN; PREFRONTAL CORTEX; RECEPTOR SUBUNITS; EXPRESSION; SCHIZOPHRENIA; WITHDRAWAL; LOCUS;
D O I
10.1038/tpj.2010.41
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The histidine triad nucleotide-binding protein-1 gene (HINT1) is implicated in schizophrenia and in the behavioral effects of morphine and amphetamine. Because nicotine dependence (ND) is highly comorbid with schizophrenia and other substance abuse, we examined the association of HINT1 with ND. Association analyses from two independent samples show that HINT1 gene variants are associated with ND phenotypes. Furthermore, human postmortem mRNA expression shows that smoking status and genotype influence HINT1 expression in the brain. In animal studies, western blot analyses show an increase of HINT1 protein level in the mouse nucleus accumbens (NAc) after chronic nicotine exposure. This increase was reduced after treatment with the nicotinic-receptor antagonist mecamylamine, and 24 and 72 h after cessation of nicotine treatment. These results indicate a genetic association between HINT1 variants and ND, and indicate that nicotine-induced modulation of HINT1 level may be involved in mechanisms of excess smoking. The Pharmacogenomics Journal (2011) 11, 251-257; doi:10.1038/tpj.2010.41; published online 1 June 2010
引用
收藏
页码:251 / 257
页数:7
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