A group of common genetics variants that affect the nicotine receptors in the nervous system could significantly increase the risk of developing nicotine addiction. These results, which could have powerful implications for policy preventing tobacco use in young people, were published on July 11, 2008 in the open-access journal PLoS Genetics.

Single nucleotide polymorphisms (SNPs) are variations in the genetic sequence that involve a single unit of DNA. A haplotype is a set of SNPs that are often linked together.

To study the effects of various haplotypes on nicotine addiction, the researchers, from the University of Utah and the University of Wisconsin, examined 2,827 long-term European American smokers in Utah and Wisconsin in the National Heart, Lung, and Blood Institute’s Lung Health Study. The level of nicotine dependence for each subject was evaluated, along with the age they began smoking daily, the number of years they smoked, and the average number of cigarettes each smoked daily. Additionally, DNA samples were collected from all smokers, and the occurrence of several common SNPs, which had already been grouped into haplotypes,which had been previously identified in a subset of the participants.

One haplotype related to the nicotine receptor in neurons put European American smokers at a greater risk of heavy nicotine dependence as adults if they began smoking daily before reaching 17 years. Specifically, people who began smoking before 17 years with two copies of this haplotype had between a 1.6- and 5-fold increase in risk of heavy smoking as an adult. This haplotype did not significantly increase the risk of addiction in adulthood for those who began smoking daily after reaching 17 years. A second haplotype instead reduced the risk of heavy nicotine dependence as an adult for those one smoked as a youth.

This genetic influence is likely valid despite the possible confounding ethnicity of the addicted smokers. According to lead author Robert Weiss, Ph.D., professor of human genetics at the University of Utah, says: “We know that people who begin smoking at a young age are more likely to face severe nicotine dependence later in life. This finding suggests that genetic influences expressed during adolescence contribute to the risk of lifetime addiction severity produced from the early onset of tobacco use.”

According to Dr. Nora Volkow, Director of the National Institute on Drug Abuse (NIDA), points out that this is an important study investigating the interactions of genetic factors with individual behaviors. “This study adds to recent advances in understanding how genetic variation can affect susceptibility to nicotine addiction, success or failure of smoking cessation treatments, and the risk of disease associated with tobacco use,” she says. “As we learn more about how both genes and environment play a role in smoking, we will be able to better tailor both prevention and cessation programs to individuals.”

A Candidate Gene Approach Identifies the CHRNA5-A3-B4 Region as a Risk Factor for Age-Dependent Nicotine Addiction.
Weiss RB, Baker TB, Cannon DS, von Niederhausern A, Dunn DM, et al.
PLoS Genet 4(7): e1000125.
doi:10.1371/journal.pgen.1000125
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Written by Anna Sophia McKenney