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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

Madden, Heath & Martin, 1997), suggesting that smoking induces increased
alcohol metabolism. While studies have not focused on whether genetic
variation in CYP2E1 alters the risk for smoking per se, an intriguing association
between a CYP2E1 polymorphism and levels of the nicotine metabolite
cotinine suggests that CYP2E1, directly or indirectly, may alter smoking and/
or nicotine/cotinine metabolism (Yang et al., 2001). The determination of a
role for genetic variation in CYP2E1 in the risk for smoking is currently being
investigated (Howard et al., 2002).
Chronic ethanol consumption results in the induction of CYP2E1, which
is believed to play an important role in the pathogenesis of alcohol-induced
liver disease and is responsible for the increased rates of ethanol metabolism
observed in those consuming relatively high amounts of alcohol (Oneta et
al., 2002). Genetic variants of CYP2E1 can alter the relative inducibility, which
may alter the impact on risk for alcohol dependence, or the resulting hepatic
damage (Lucas et al., 1995; Ueno et al., 1996).

Genetics of opioid dependence

Heritability of opioid dependence
Heritability for opioid dependence is high, estimated at almost 70% (Tsuang
et al., 2001). Twin studies consistently find higher concordance for opiate
dependence in monozygotic than in dizygotic twins, indicating a significant
genetic contribution (Lin et al., 1996; Tsuang et al., 1996;1999; 2001). Genetic
risk for dependence can be divided into a common, or shared, vulnerability
across different classes of drugs, and a genetic vulnerability to the specific
drug in question. Opiate dependence has the lowest extent of common
vulnerability to substance dependence, at 50%, indicating that there may be
specific opiate-related neurochemical components to heroin dependence.
It is clear from the above, that opiate use and dependence are at least in part
influenced by genetic factors.

Opioid dependence and linkage studies
There have been no family-based genetic linkage studies of opioid
dependence in humans.

Candidate genes for opioid dependence

The candidate gene approach requires the selection of genes with perceived
relevance to the trait in question. In the case of opioids this is easy, as the
receptor pharmacology is well understood and there are consequently good
candidate genes from the endogenous opioid system. Data from genetic
epidemiology tell us that the highest genetic contribution to opioid
dependence is from unique genetic effects – i.e. those not connected with

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