Genetic differences help explain cigarette addiction


By Roxanne Khamsi


Two studies of smokers have yielded new insight into a gene linked to cigarette addiction. The findings could lead to more personalised - and ultimately more effective - treatments that help people to quit smoking.

Both groups examined the numerous forms of a gene called CYP2A6, which codes for an enzyme that acts mostly in the liver and regulates nicotine metabolism in the body. Previous research revealed that people with an ineffective form of the gene are less likely to become addicted to smoking.

Experts think that nicotine levels remain elevated for longer in these individuals, delaying the craving for the next cigarette. Nicotine is the primary chemical responsible for smoking addiction.

People carry different forms of the CYP2A6 gene, and this is more pronounced in particular parts of the world. "It seems that there's more variation in this gene in Asian populations," says Sharon Murphy of the University of Minnesota in Minneapolis, US, who has studied nicotine metabolism.

Nicotine patches

Researchers in Tokyo decided to compare how different forms of the gene influenced the cigarette consumption of 200 Japanese people aged 50 or over who smoked 20 cigarettes (one pack) or more each day. The scientists found that roughly one-quarter of the participants carried two copies of the normal form of the gene, CYP2A6*1 and that these people smoked the most - almost two packs a day on average.

Smokers who carried two copies of the CYP2A6*4 gene, which results in slower nicotine metabolism, smoked the least. The study also provided new details about the role of other forms of the gene - CYP2A6*7 and CYP2A6*9 - suggesting these also reduce cigarette consumption.

Another new study has found that variation in the CYP2A6 gene can affect the nicotine levels people receive from nicotine patches often used to help quit smoking. Rachel Tyndale of the University of Toronto, Canada, found that slow metabolisers of nicotine had higher levels of nicotine in their blood when using the patches compared with faster metabolisers.

The findings suggest that people with the genes for fast nicotine metabolism may need more of the chemical to calm their cravings and help them kick their habit.

"If you can identify an individual who metabolises nicotine faster you can treat them more effectively," says Murphy. "Even two to three patches is way better than the cigarettes."

Journal reference: European Respiratory Journal (DOI: 10.1183/09031936.06.00056305), Molecular Psychiatry (DOI:10.1038/


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