Association of the serotonin transporter gene with smoking behavior.
OBJECTIVE
In an ongoing molecular genetic study of temperament, participants were genotyped to examine the association of smoking with two polymorphisms of the serotonin transporter gene (SERT): the promoter region, 5-HTTLPR, and an intronic variable-number-of-tandem-repeats region (VNTR).


METHODS
Full information was available for 330 families, and 244 "ever smokers" were identified (54 past smokers, 190 current smokers). The average number of cigarettes smoked per day was 13.12, and the mean Fagerstrom Tolerance Questionnaire score was 4.79. Associations of genotype, Tridimensional Personality Questionnaire scores, and smoking phenotype were tested by using a robust family design with a variance-components framework and by case-control analysis.


RESULTS
There was a significant excess of the 5-HTTLPR long allele with the 12-repeat VNTR in current smokers, past smokers, and ever smokers, compared to participants who had never smoked. The results from the population design were confirmed in the family-based analysis. No association was observed between two quantitative measures of smoking and the polymorphisms. A weak association was observed between novelty seeking and the VNTR polymorphism and between reward and 5-HTTLPR. Smokers, regardless of gender, scored significantly higher on novelty seeking and did not differ on harm avoidance or reward.


CONCLUSIONS
There was a highly significant association between SERT and the categorical definition of smoking, irrespective of dependence level, suggesting that this gene influences the initiation of smoking. Mediation analysis failed to substantiate the hypothesis that novelty seeking partially mediates the effect of SERT on smoking. SERT appears to independently contribute to novelty seeking and smoking.
Kremer
Ilana
I
Department of Psychiatry, Emek Hospital, Afula, Israel.
Bachner-Melman
Rachel
R
Reshef
Alon
A
Broude
Leonid
L
Nemanov
Lubov
L
Gritsenko
Inga
I
Heresco-Levy
Uriel
U
Elizur
Yoel
Y
Ebstein
Richard P
RP
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D012701:Serotonin / Q000235:genetics* / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins; D012737:Sex Factors; D012907:Smoking / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D013694:Temperament / Q000502:physiology
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin