The role of the serotonin transporter gene in cigarette smoking.
Data from twin studies have suggested that cigarette smoking has a significant heritable component. The serotonin transporter gene (5-HTT) is a plausible candidate gene for smoking predisposition because of its association with psychological traits relevant to smoking behavior. The present investigation evaluated the associations of smoking practices and smoking cessation with a common polymorphism in the upstream regulatory region of 5-HTT that is manifested as either an inserted (long) variant or a deleted (short) variant. The short variant of the polymorphism is associated with reduced transcription of the gene promoter and diminished uptake. A case-control study design (268 smokers and 230 controls) was used to evaluate the associations of 5-HTT genotype with smoking status. Case series analysis of smokers was used to evaluate the role of 5-HTT in age at smoking initiation, previous quitting history, current smoking rate, and 12-month quit rate following a minimal-contact smoking cessation program. There were no significant differences in the distribution of 5-HTT genotypes in smokers as compared with 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 distribution of 5-HTT genotypes: Caucasians were significantly more likely to carry the short variant of the 5-HTT gene than were African Americans (P = 0.005). These findings suggest that the 5-HTT gene may not play a significant role in cigarette smoking practices.
Lerman
C
C
Cancer Genetics Program, Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007-4104, USA.
Shields
P G
PG
Audrain
J
J
Main
D
D
Cobb
B
B
Boyd
N R
NR
Caporaso
N
N
D000328:Adult; D044383:Black People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D012907:Smoking / Q000235:genetics*; D016540:Smoking Cessation; D044465:White People / Q000235:genetics; D001741:Black or African American
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins