COMT Gene and Tobacco Use Disorder

Nicotine replacement therapy uses products that supply low doses of nicotine. The goal of therapy is to cut down on cravings for nicotine and ease the symptoms of nicotine withdrawal. Nicotine replacement therapy is of the most help for people who smoke more than 15 cigarettes a day. It is not yet proven to help people who smoke fewer than 10 cigarettes per day. A study1 showed that COMT polymorphisms are associated with the outcomes following smoking cessation treatment with nicotine.

Catechol-O-methyltransferase (COMT) is one of the major degradative pathways of dopamine and COMT Val/Met polymorphisms are associated with the enzyme activity, which is related to dopamine involvement in the nicotine addiction process1. A functional polymorphism in this gene has also been demonstrated to be related to processing of emotional stimuli and pain regulation in healthy subjects.

COMT rs4680 (Val158Met) is a well studied SNP in the COMT gene. The wild-type allele is a (G), coding for a valine amino acid; the (A) substitution polymorphism changes the amino acid to a methionine. This alters the structure of the resultant enzyme such that its activity is only 25% of the wild type.

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