By Patrick Zickler, NIDA NOTES Staff Writer
Each day more than 3,000 young people smoke their first cigarette, and the likelihood of becoming addicted to nicotine is higher for these young smokers than for those who begin later in life. A number of biological, social, and environmental factors combine to influence smoking initiation, and NIDA-supported research suggests that genetic factors play a role in determining a smoker's susceptibility to nicotine addiction. (See "Evidence Builds That Genes Influence Cigarette Smoking".) Now, researchers at the University of Pennsylvania in Philadelphia and Virginia Commonwealth University in Richmond have found an association between smoking initiation and variations in a gene related to the brain's serotonin system, which is involved in mood and behavior.
Researchers at the University of Pennsylvania
have found that women and men who inherit the "A" form (allele)
of the tryptophan hydroxylase gene from both parents and who
become smokers are likely to begin smoking at an earlier age
than women and men who inherit the "C" allele.
in Gene May Affect Likelihood of
Smoking at Early Age
At the NIDA-supported Transdisciplinary Tobacco Use Research Center at
the University of Pennsylvania, Dr. Caryn Lerman and her colleagues investigated
the possible relationship between smoking behavior and different forms
(alleles) -- designated 779A and 779C -- of a gene that regulates tryptophan
hydroxylase (TPH), an enzyme involved in the synthesis of serotonin. "There
is evidence from previous studies linking the less common 779A allele
with behaviors related to poor impulse control," Dr. Lerman says. "Because
of the association of tobacco and other substance use with poor impulse
control, we speculated that the TPH gene may play a role in smoking initiation
To investigate this possibility, the researchers recruited 249 smokers
(smoked at least 5 cigarettes per day for the past year) and 202 nonsmokers
(smoked fewer than 100 cigarettes in their lifetime). All the participants
were white; their average age was 44 years, and slightly more than half
(56 percent) were women. All participants completed written questionnaires
that provided information on their age, education, marital status, and
certain psychological traits. Smokers provided smoking histories, including
the age when they started smoking at least one cigarette per day.
The researchers tested samples of the participants' blood to determine whether they had the 779A or 779C alleles for the TPH gene. The overall allele frequency was 42 percent for the THP 779A allele and 58 percent for the 779C allele. There was no significant association of the presence or absence of the 779A allele with becoming a regular smoker, Dr. Lerman says. But among participants who did become smokers, the 779A allele was associated with the age at which they began smoking. Those who inherited copies of 779A from both parents started smoking at age 15.6 years, those with one A and one C allele began smoking at 17.1, and those with two copies of 779C began smoking at 17.3 years.
"In light of other findings that 779A is associated with poor impulse control, one interpretation of this study is that individuals with that allele may be prone to engage in risky behavior such as smoking initiation at an earlier age," Dr. Lerman says.
Dr. Lerman discussed her research results with Dr. Patrick Sullivan at Virginia Commonwealth University. Dr. Sullivan and his colleagues then developed a study to look for possible associations between the TPH 779A allele and smoking initiation in a group of 740 participants who had previously been enrolled in research dealing with genetic influences on a range of behaviors, including drug abuse and addiction. As part of the earlier study, the participants had completed extensive questionnaires that included information about smoking, including age at which smoking began, age at which smokers first became dependent on nicotine (suffered withdrawal if they tried to quit), and the severity of their dependence -- measured by a standard tool cal