Association between DRD2/ANKK1 Taq1A genotypes, depression and smoking cessation with nicotine replacement therapy

Tobacco dependence and depression are believed to have a common familial component, most probably genetic, and mood disorders have been reliably associated with failure to stop smoking. Variant genotypes of the Taq1A (DRD2/ANKK1, 32806T, rs1800497) polymorphism have been associated with failure to stop smoking in some studies, but not others. We investigated the association between Taq1A genotypes and smoking cessation, while also considering mental health.

This was a prospective study in 419 smokers who attended a smoking cessation clinic and used standard doses of nicotine replacement therapy. DNA samples and baseline measures including demographics, severity of tobacco dependence, mental health history and history of drug misuse were taken. Smoking cessation at the end of treatment was biochemically verified using expired-air carbon monoxide.

We found no simple relation between Taq1A genotype and smoking cessation, although the association between cessation and lifetime depression was significantly modified by genotype. The relationship was such that for those having only common alleles there was no association between depression and stopping smoking, whereas for those with at least one variant allele (A1A2/A1A1) depression was associated with a two-fold reduction in the likelihood of stopping.

Those having a Taq1A variant allele and a history of depression are likely to experience particular difficulty when trying to stop smoking and may require treatment other than standard doses of nicotine replacement. This finding might explain previous conflicting results for Taq1A and smoking cessation in studies where depression history was not measured, and may help to explain the underlying link between depression and smoking.