An association study of DRD5 with smoking initiation and progression to nicotine dependence

A large body of genetic epidemiological data strongly implicate genetic fac tors in the etiology of smoking behavior. Polymorphisms of genes in the dop aminergic system are plausible functional candidate genes and a linkage and an association study suggested that the type 5 dopamine receptor gene (DRD 5) may be etiologically involved. We investigated the association of four D RD5 polymorphisms with smoking initiation and progression to nicotine depen dence in a population-based sample of over 900 subjects. For smoking initia tion, there was no significant association with the four DRD5 markers we st udied; however, maximum likelihood analyses suggested the presence of a hap lotype protective against smoking initiation. For progression to nicotine d ependence, there were no strongly significant associations with the four DR D5 markers or for the estimated haplotypes, These data are not consistent w ith a strong etiological role for DRD5 in the etiology of these complex smo king behaviors. (C) 2001 Wiley-Liss, Inc.