Abstract
PurposeThis study investigated whether a gene polymorphism causing a Val66Met substitution (rs6265) in brain-derived neurotrophic factor (BDNF) is associated with smoking initiation, smoking cessation, nicotine dependence and age of smoking initiation, in Japanese participants. Additionally, this study examined whether the S allele of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) is associated with the BDNF Val66Met polymorphism on smoking phenotypes. Patients and methodsThe genotypic proportion of the polymorphism responsible for BDNF Val66Met was determined in 148 participants including 88 current smokers, 21 former smokers, and 39 never smokers, and Fisher's exact test was used to investigate the relationship between this polymorphism and smoking cessation and initiation as well as the association between the genotypes of current smokers with a heavy smoking index (HSI) and the age of smoking initiation. In addition to the BDNF Val66Met polymorphism, the 5-HTTLPR polymorphism has also been evaluated in a specific subset of participants. ResultsWe found statistically significant correlations between the BDNF Val66Met polymorphism and the HSI, both in the whole study sample (P = 0.017) and in the male subgroup (P = 0.049). Moreover, the 5-HTTLPR polymorphism was associated with the age of smoking initiation in current smokers carrying the BDNF Met allele, in both the whole study sample (P = 0.041) and the male subgroup (P = 0.041). On the other hand, no association was observed between the BDNF Val66Met polymorphism, either alone or in combination with the 5-HTTLPR polymorphism, and the age of smoking cessation. Finally, no independent effects of the BDNF Val66Met genotype on the age of smoking initiation were detected. ConclusionThis pilot study provides preliminary findings regarding the influence of BDNF Val66Met on smoking phenotypes and the interacting effect of 5-HTTLPR on the association between BDNF Val66Met and smoking phenotypes in Japanese participants.
Highlights
Recent genome-wide association studies have identified associations between common allelic variants and smoking phenotypes [1, 2]
Nicotine dependence was estimated using the Heaviness of Smoking Index (HSI) [18], which was calculated by summing the two scores of the time to smoke the first cigarette of the day after awakening and the number of cigarettes smoked per day
A total of 148 Japanese participants were enrolled in our study (Table 1), including 88 current smokers, 21 former smokers, and 39 never smokers
Summary
Recent genome-wide association studies have identified associations between common allelic variants and smoking phenotypes [1, 2]. The brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism has been found to be strongly related to smoking initiation, as reported by the Tobacco and Genetics Consortium [3]. High levels of BDNF mRNA are expressed in dopaminergic neurons projecting from the ventral tegmental area to the nucleus accumbens [4]. BDNF potentiates dopamine release in the nucleus accumbens through activation of the dopaminergic nerve terminals [5]. Several studies have investigated the associations of BDNF Val66Met with smoking behavior and nicotine dependence. Lang et al [6] reported a significantly higher Met allele proportion among smokers than among never smokers in a Caucasian sample, the association appeared to be male-sex specific [7]. Montag et al [8] were unable to replicate this positive association in large samples of Caucasians
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