Association of polymorphisms of the serotonergic system with smoking initiation in Caucasians
Received 7 July 2009; received in revised form 31 October 2009; accepted 17 November 2009.
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-HT2C 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-HT2C −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-HT2C −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-HT2C receptor gene polymorphisms and smoking initiation in male Caucasian subjects.
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