Association of polymorphisms of the serotonergic system with smoking initiation in Caucasians.
BACKGROUND
The serotonergic system may be implicated in susceptibility to nicotine dependence as nicotine increases 5-hydroxytryptamine (5-HT) release in brain and symptoms of nicotine withdrawal may be modulated by diminished serotonergic neurotransmission. We examined the association of polymorphisms of genes involved in release and receptor function of 5-HT with cigarette smoking initiation in subjects of Caucasian origin.


METHODS
5-HTTLPR polymorphism of the 5-HT transporter gene and -759C/T (rs3813929) and -697G/C (rs518147) polymorphisms of the 5-HT(2C) receptor gene were analyzed in 172 smoking initiators and 254 non-initiators, using PCR-RFLP method. Smoking behavior was assessed with a questionnaire about tobacco use.


RESULTS
We found no differences in the frequency of the 5-HTTLPR genotypes between smoking initiators and non-initiators. However, the frequency of 5-HT(2C) -759T allele was significantly higher in non-initiators than smoking initiators (29.5% vs 16.3%, p=0.002) and the same was true for 5-HT(2C) -697C allele carriers (48.8% vs 34.9%, p=0.004). Sex-dependent analysis revealed that these increased frequencies of -759T and -697C allele carriers were present only in males. No association was observed between any quantitative measures of smoking and these three polymorphisms.


CONCLUSIONS
5-HTTLPR polymorphism was not associated with smoking initiation in either male or female subjects. However, significant association was found between 5-HT(2C) receptor gene polymorphisms and smoking initiation in male Caucasian subjects.
Iordanidou
Maria
M
Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, Alexandroupolis 68100, Greece.
Tavridou
Anna
A
Petridis
Ioannis
I
Kyroglou
Soultana
S
Kaklamanis
Loukas
L
Christakidis
Dimitrios
D
Manolopoulos
Vangelis G
VG
D017668:Age of Onset; D000368:Aged; D000483:Alleles; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006115:Greece / Q000453:epidemiology; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics; D012701:Serotonin / Q000235:genetics* / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012907:Smoking / Q000453:epidemiology* / Q000235:genetics*; D009435:Synaptic Transmission; D044465:White People
D044405:Receptor, Serotonin, 5-HT2C; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D004247:DNA