Pleiotropic effect of the TPH A779C polymorphism on nicotine dependence and personality.

Recent studies from molecular genetics have suggested an association between the tryptophan hydroxylase 1 (TPH1) gene and nicotine addiction indicating a dysfunction of the serotonergic (5-HT) system in smoking behavior. In a sample of 252 healthy subjects, a significant association between variations observed in nicotine dependence and the heterozygous AC-genotype of the TPH A779C polymorphism could be demonstrated. Moreover, the heterozygous genotype was significantly associated with a personality trait of neurotic aggression (indirect hostility, negativism), as measured by the Buss-Durkee-Hostility-Inventory (BDHI). The positive heterosis effects with respect to nicotine addiction and personality support the idea that the TPH1 gene exerts pleiotropic effects.