THE ROLE OF THE SEROTONIN TRANSPORTER GENE IN CIGARETTE-SMOKING

Data from twin studies have suggested that cigarette smoking has a sig nificant heritable component, The serotonin transporter gene (5-HTT) i s a plausible candidate gene for smoking predisposition because of its association with psychological traits relevant to smoking behavior, T he present investigation evaluated the associations of smoking practic es and smoking cessation with a common polymorphism in the upstream re gulatory region of 5-HTT that is manifested as either an inserted (lon g) variant or a deleted (short) variant, The short variant of the poly morphism is associated with reduced transcription of the gene promoter and diminished uptake, A case-control study design (268 smokers and 2 30 controls) was used to evaluate the associations of 5-HTT genotype w ith smoking status, Case series analysis of smokers was used to evalua te the role of 5-HTT in age at smoking initiation, previous quitting h istory, current smoking rate, and 12-month quit rate following a minim al-contact smoking cessation program, There were no significant differ ences in the distribution of 5-HTT genotypes in smokers as compared wi th nonsmokers in either Caucasians or African Americans, nor was the 5 -HTT genotype associated with the smoking outcome variables, However, the results did reveal significant racial differences in the distribut ion of 5-HTT genotypes: Caucasians were significantly more likely to c arry the short variant of the 5-HTT gene than mere African Americans ( P = 0.005), These findings suggest that the 5-HTT gene may not play a significant role in cigarette smoking practices.