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 process.
The common methionine (met) for valine (val) at codon 158 (val(158)met) polymorphism in the catechol-O-methyltransferase (COMT) gene has been associated with nicotine dependence, alterations in executive cognitive function, and abstinence-induced working memory deficits in smokers.
In pairwise interaction analysis of SNPs from the two loci (COMT SNP-CHRNA5-CHRNA3 SNP), the interaction of intronic COMT SNP, rs9332377, with CHRNA3 3'UTR SNP rs660652 was significantly associated with ND (p = 0.0005), withstanding correction for multiple testing.
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.
This study evaluates the relationship of six polymorphisms found in the CHRNA3, DRD2 and COMT genes with nicotine dependence, the ability to quit smoking and the occurrence of withdrawal symptoms after short-term use of nicotine patch in hospitalized patients.
These data suggest a novel brain-behavior mechanism that may underlie the increased susceptibility to nicotine dependence and smoking relapse associated with the COMT val allele.
In summary, our results provide evidence for a role of COMT in the susceptibility to ND and further confirm that its effect is ethnic and gender specific.