Association of polymorphisms of the serotonergic system with smoking initiation in Caucasians

Abstract 

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.

Keywords: Gender, 5-HT_2C receptor gene polymorphisms, 5-HTTLPR polymorphism, Smoking, Smoking initiation, Caucasians