GENE INFLUENCES NICOTINE ADDICTION

If your first few attempts to smoke cigarettes made you so sick that
you failed to pick up the habit, then you may be in the approximately
15 percent to 20 percent of the population carrying a gene that seems
to make people less likely to smoke.

This genetic difference alters the way some people metabolize
nicotine, making cigarettes more potent and more noxious than they are
for others, said Rachel Tyndale of the University of Toronto.

Although the gene apparently doesn't protect people from becoming
addicted to cigarettes, it may mean they are less prone to getting
hooked.

Tyndale said she hoped the finding would eventually lead to
more-fine-tuned medications aimed at helping the millions of Americans
who want to quit smoking but can't.

"I think this is a very exciting finding," said Alan Leshner, director
of the National Institute of Drug Abuse. "It's the first clear
evidence of a genetic vulnerability to addiction to nicotine, and it
gives us a mechanism behind it."

Tyndale, who published the work in today's issue of the journal
Nature, said the gene influences the amount of nicotine in the
bloodstream - the central factor that determines craving for
cigarettes in addicts.

For most smokers, the habit is driven by the desperate need to keep a
near-constant level of nicotine in the bloodstream. That's why many
smokers get such powerful cravings in the mornings, after the nicotine
levels have dropped overnight, said Tyndale, who was once herself
addicted to cigarettes. But for those with the defective gene,
nicotine levels drop more slowly, possibly reducing their craving.

The finding rests on earlier work in biochemistry that revealed that
an enzyme called CYP2A6 was responsible for breaking down molecules of
nicotine into products that could be swept out of the body. The
manufacture of this enzyme was controlled by a gene.

Tyndale found there were two versions of this gene - a more common
standard version and a less common anti-smoking (or "defective")
version, which causes people to produce only half the normal amount of
this nicotine-processing enzyme.

Tyndale drew her conclusions from a study that showed that 20 percent
of a group of 184 nonsmokers carried the anti-smoking version of this
gene while only 10 percent of a group of 244 smokers did.

For some people with the anti-smoking version, she said, cigarettes
caused too much nausea, dizziness and other discomfort to be appealing
from the start. Others go ahead and smoke, but generally need fewer
cigarettes to feel satisfied.

Thus, the gene seems to offer partial protection against becoming a
smoker.

Leshner, the institute director, points out that people vary in their
tendency to get addicted to cigarettes, alcohol and other drugs. These
differences are determined by a mishmash of many genetic and
environmental influences.

Although the gene in Tyndale's study is not the only factor
determining who will get hooked on smoking, it is one of the only ones
whose function is understood, he said.

Perhaps, Tyndale speculated, a treatment could mimic the effects of
the gene by disabling the CYP2A6 enzyme. Such a treatment might
increase the effectiveness of nicotine gums or patches, or might make
a relapse less tempting.

Checked-by: (trikydik)