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Mutations and temptations
How tiny alterations in the
genetic code are linked to a
vulnerability to addiction
BY KRISTINE KELLY
Central to the study of addiction is why one person
can walk away from a drug while another can’t. There is a solid base
of research demonstrating that people’s genes can help make the
decision to say no easy, or tough, and Mary Jeanne Kreek and her laboratory
have been exploring the genetic basis of addiction for many years. But in
new research published in the December issue of Pharmacogenetics, she is
taking her studies beyond the simple question of which genes are involved
in addiction. She’s focusing on tiny mutations within those genes.
“What we wanted to know was if small changes in
DNA have any effect on an individual’s vulnerability to develop
heroin addiction,” Kreek says.
Kreek and colleagues were looking for small mutations
called single nucleotide polymorphisms (SNPs). These are DNA sequence
variations between different people, where only a single nucleotide
building block — A, T, G or C — is altered. Some SNPs do not
alter the sequence of the protein, but can affect aspects like its
stability and regulation, perhaps enough to change an individual’s
susceptibility to addiction.
“The human kappa opioid receptor has a role in
both opiate withdrawal and responses to cocaine,” says Vadim Yuferov,
the study’s first author and a senior research associate in
Kreek’s lab. “But its full structure hadn’t been studied,
so that’s where we started.”
“After we clarified the sequence of the kappa
gene,” says Kreek, “we looked at the groups of people
represented in New York. We sequenced the kappa gene in close to 300 people
from different ethnic backgrounds and thus far have found 12
SNPs.”
Three had already been identified during
Yuferov’s initial sequencing. Of the remaining nine, however, one
stood out from the rest. A small nucleotide change from a G to a T resulted
in a statistically significant increase in an individual’s
vulnerability to heroin addiction. While significant across all ethnic
groups, some had stronger associations than others.
“The study needs to be replicated, but the
results of this study and others already tell us that SNPs have a role in
addiction,” says Kreek. “If you consider that there are
multiple SNPs in multiple genes, all interacting with environmental
factors, an individual’s vulnerability could be greatly increased or
decreased. Understanding how SNPs affect addiction will eventually lead to
the design of more effective pharmacotherapies, as well as tools for better
preventative measures for individuals at risk.”
May 13, 2005
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