Association of the histidine-triad nucleotide-binding protein-1 (HINT1) gene variants with nicotine dependence.
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.
Department of Psychiatry and Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
K J
KJ
Jackson
Q
Q
Chen
J
J
Chen
S H
SH
Aggen
K S
KS
Kendler
X
X
Chen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001344:Autopsy; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D057507:Mice, 129 Strain; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D018722:Nicotinic Agonists / Q000009:adverse effects*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D012907:Smoking / Q000235:genetics*; D013997:Time Factors; D014029:Tobacco Use Disorder / Q000235:genetics*; D014768:Virginia; D055815:Young Adult
C063306:HINT1 protein, human; C489275:Hint1 protein, mouse; D009419:Nerve Tissue Proteins; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D012333:RNA, Messenger; D008464:Mecamylamine