Tryptophan hydroxylase gene variant and smoking behavior

Approximately 50% of the variance in smoking behavior is attributable to ge netic factors. Genes in the serotonin system are plausible candidates becau se of serotonin's role in mood regulation. The present study examined the a ssociation of smoking behavior with a polymorphism in the TPH gene, which c odes for a rate limiting enzyme in the biosynthesis of serotonin. A polymor phism in intron 7 has been linked with a variety of traits involving poor i mpulse control. Participants in this study were 249 Caucasian smokers and 2 02 nonsmokers recruited through newspaper advertisements. Smokers completed smoking history and nicotine dependence assessments. The overall frequenci es of the A- and C-allele were 42% and 58%, respectively. There was no asso ciation of TPH alleles with smoking status. However, case series analysis i ndicated that individuals with the A/A genotype started smoking at age 15.6 years, compared with 17.3 years among smokers with other genotypes. This a ssociation was significant in a multivariate regression model controlling f or age, education, body mass index (BAH), alcohol use, and medication use. This finding is consistent with previous studies relating the A-allele to i mpulsive behavior and suggests that it may predispose to early smoking init iation. Future family-based studies are needed to con-firm this finding. Pu blished 2001 Wiley-Liss, Inc(dagger).