Association between dependent smoking and a polymorphism in the tyrosine hydroxylase gene in a prospective population-based study of adolescent health.

This study reports pilot data on an association between tobacco dependence and a five-allele tetranucleotide repeat polymorphism in the first intron of the tyrosine hydroxylase (TH) gene. One hundred and twenty-six Australian adolescents who had participated in the Health in Transition Study (1993-1997), and who showed patterns of either dependent or nondependent smoking across four waves of data collection, consented to participation in the pilot study. The smoking status of those recruited was confirmed using a telephone-administered drug use questionnaire during 2000. Tobacco dependence was defined as smoking more than 6 days per week and more than 10 cigarettes per day during wave 5 (year 2000) and at least one prior wave ( n = 58). A second, more stringent phenotype included smoking within an hour of waking ( n = 37). The control group comprised adolescents who had used tobacco but had remained low-level social smokers across each wave of data ( n = 56). DNA was collected using a mouthwash procedure. Using the more strictly defined tobacco dependence phenotype, and after adjusting for sex, a significant protective association was found between the K4 allele and tobacco dependence (OR 0.27, 95% confidence interval [CI] 0.09, 0.82). No association was found using the liberal criteria of tobacco dependence (OR 0.51, 95% confidence interval [CI] 0.23, 1.2). These preliminary results replicate a previous association between tobacco use and the K4 allele of the TH gene (Lerman et al., 1997). The potential significance of including time to first cigarette in definitions of tobacco dependence and the possible role that these TH variants might play in tobacco dependence are discussed.