Association of functional dopamine-beta-hydroxylase (DBH) 19 bp insertion/deletion polymorphism with smoking severity in male schizophrenic smokers

Recent evidence suggests that a dopamine beta-hydroxylase (DBH) polymorphism may play a role in determining an individual's predisposition to developing nicotine dependence. The mechanism for such an association may reflect nicotine's mediation of drug reward in the brain through actions on dopamine, a key mediator of drug reward. Because schizophrenia patients have usually high rates of nicotine use, they are a model group to study such an association. In this study, we hypothesized that the functional polymorphism of DBH (DβH5′-Ins/Del) was associated with smoking in patients with schizophrenia. This polymorphism was genotyped in 636 chronic male schizophrenia (smoker/nonsmoker = 490/146) and 396 male controls (smoker/nonsmoker = 231/165) using a case–control design. The cigarettes smoked per day (CPD) and smoking behaviors were evaluated by clinician-administered questionnaires and the Fagerstrom Test for Nicotine Dependence (FTND). The results showed no significant differences in DBH 5′-Ins/Del genotype and allele distributions between the patients and healthy controls or between smokers and nonsmokers in either patients or healthy controls alone. However, schizophrenic smokers with the Del allele smoked fewer cigarettes each day and had lower FTND score than those with Ins/Ins genotype. These results suggest that the DBH 5′-Ins/Del polymorphism may influence smoking severity among schizophrenic smokers.