The lack of association between catechol-O-methyl-transferase Val108/158Met polymorphism and smoking in schizophrenia and alcohol dependence.

Patients with schizophrenia and alcohol dependence are often smokers. There are inconsistencies across the literature on the relationship between the functional catechol-O-methyl-transferase (COMT) Val108/158Met polymorphism and smoking and/or nicotine dependence (Redden et al., 2005; Tammimaki and Mannisto, 2010). The study elucidated the association between the COMT Val108/158Met polymorphism and smoking in 828 ethnically homogeneous non-related Caucasian patients with schizophrenia (40.3712.6 years old), 616 patients with alcohol dependence (49.7710.2 years old), diagnosed with the Structured Clinical Interview for DSM-IV, and in 1058 healthy control subjects (40.5715.3 years old). The COMT Val108/158Met polymorphism was genotyped using a Taqman-based allele-specific polymerase chain reaction assay (Applied Biosystems, Foster City, CA, USA). COMT genotypes in the studied groups were in Hardy– Weinberg equilibrium. The present smoking status differed significantly (w1⁄4327.71; Po0.001) between the studied groups, since male patients with schizophrenia smoked more frequently, while healthy control women smoked less frequently than other subjects. The stepwise logistic regression (odds ratio (OR)1⁄41.56, 95% confidence interval (CI)1⁄41.10–2.23, P1⁄40.014) and the w test (Table 1) revealed that the COMT Val/Val genotype was significantly associated with smoking in healthy male subjects, since carriers of one (w1⁄45.686; P1⁄40.017) or two (w1⁄49.783; P1⁄40.008) Val alleles were more frequently current smokers. The significant association between smoking, age and gender, with no interaction between smoking and COMT Val108/158Met variants in patients with schizophrenia and alcohol dependence, might be explained by the different effects of nicotine on social and interpersonal factors in psychiatric versus healthy subjects, or by the different interactions between dopamine activity and nicotine in the regions involved in the regulation of the reward pathways in healthy opposed to subjects with schizophrenia and alcohol dependence. Although the hypothesis of the study was that COMT Val108/158Met genotypes would be significantly associated with smoking in schizophrenia and alcohol dependence, our study, with a sufficiently large sample size (N1⁄42502) and power (higher than 0.800), with subjects matched for the first time the lack of a significant association between smoking and the COMT Val108/158Met polymorphism in schizophrenia, and confirmed no association between smoking and the COMT Val108/158Met polymorphism in alcoholism (Foroud et al., 2007). In line with previous results obtained in smaller groups