Effect of genetic polymorphism of brain-derived neurotrophic factor and serotonin transporter on smoking phenotypes: A pilot study of Japanese participants

PURPOSE: This 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 METHODS: The 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. RESULTS: We 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. CONCLUSION: This 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.