Background
A nonsynonymous coding polymorphism, rs16969968, of the CHRNA5 gene that encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR)
has been found to be associated with nicotine dependence. The goal of this study was
to examine the association of this variant with cocaine dependence.
Methods
Genetic association analysis was performed in two independent samples of unrelated
case and control subjects: 1) 504 European Americans participating in the Family Study
on Cocaine Dependence (FSCD) and 2) 814 European Americans participating in the Collaborative
Study on the Genetics of Alcoholism (COGA).
Results
In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (odds ratio = .67 per allele, p = .0045, assuming an additive genetic model), but in the reverse direction compared
with that previously observed for nicotine dependence. In multivariate analyses that
controlled for the effects of nicotine dependence, both the protective effect for
cocaine dependence and the previously documented risk effect for nicotine dependence
were statistically significant. The protective effect for cocaine dependence was replicated
in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype
for nicotine dependence, were consistent with those observed in FSCD.
Conclusions
The minor (A) allele of rs16969968, relative to the major G allele, appears to be
both a risk factor for nicotine dependence and a protective factor for cocaine dependence.
The biological plausibility of such a bidirectional association stems from the involvement
of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward
pathways.
Key Words
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Article info
Publication history
Published online: June 03, 2008
Accepted:
April 5,
2008
Received in revised form:
March 19,
2008
Received:
December 4,
2007
Identification
Copyright
© 2008 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
