Association study of a functional catechol-O-methyltransferase polymorphism and smoking in healthy Caucasian subjects.

Tobacco smoking is a global health problem. The association of a functional common polymorphism in the catechol-o-methyltransferase gene (COMT Val158Met) with smoking behavior has been extensively studied, but with divergent findings. In the present study the frequency of COMT genotypes and alleles was evaluated in 578 male and a smaller group of 79 female unrelated, medication-free Caucasian healthy subjects of Croatian origin. Smokers were classified as subjects smoking <or=10 cigarettes per day, while subjects who never smoked in their life were regarded as nonsmokers. A chi(2)-test with standardized residuals and Bonferroni correction revealed significant (P=0.017) differences in Met/Met, Met/Val or Val/Val genotype frequency between male smokers and nonsmokers. This significant association between COMT Val158Met polymorphism and smoking was not detected in female subjects, due to the small number of women, which represents a limitation of the study. Our results confirmed the significant association between COMT variants and smoking, which was due to the higher frequency of Val/Val homozygotes in male smokers compared to male nonsmokers. These results suggest that carriers of the high activity COMT variant are more prone to develop a higher level of nicotine dependence, or that they release more dopamine than carriers of Met/Met or Met/Val genotypes.