title: Nicotine dependence in a prospective population-based study of adolescents: the protective role of a functional tyrosine hydroxylase polymorphism.
abstract: Dopamine is a key neurotransmitter of the mesolimbic reward pathway in the human brain, and tyrosine hydroxylase (TH) is the rate-limiting enzyme in dopamine biosynthesis. Consequently, the gene encoding TH is a strong candidate for involvement in the genetic component of addiction. The importance of this gene in nicotine dependence is supported by many studies showing a link between nicotine administration and TH expression. A functional tetranucleotide repeat polymorphism within intron 1 of the TH gene (HUMTH01-VNTR) has been shown to modify tobacco use in two independent Caucasian samples from the USA and Australia. Using information drawn from an eight-wave Australian population-based longitudinal study of adolescent health, we tested the effect of the HUMTH01-VNTR on nicotine dependence. Comparisons were made between dependent smokers and non-dependent smokers. These data provide further support for a protective association between the K4 allele and dependent smoking (odds ratio 0.54, 95% confidence interval 0.28-1.0). No associations were observed at any of three other common TH polymorphisms (rs6356, rs6357 and HUMTH01-PstI). Including these data, three independent studies, two of which use identical phenotypes, have now identified a protective relationship between the K4 allele of the functional HUMTH01-VNTR polymorphism and high-level smoking.
authors.affiliation: Behavioural Genetics Laboratory, Murdoch Childrens Research Institute, Royal Children's Hospital,University of Melbourne, Parkville, Melbourne, Australia. ric.anney@mcri.edu.au
authors.forename: Richard J L
authors.initials: RJ
authors.lastname: Anney
authors.forename: Craig A
authors.initials: CA
authors.lastname: Olsson
authors.forename: Mehrnoush
authors.initials: M
authors.lastname: Lotfi-Miri
authors.forename: George C
authors.initials: GC
authors.lastname: Patton
authors.forename: Robert
authors.initials: R
authors.lastname: Williamson
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D015331:Cohort Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics*; D018598:Minisatellite Repeats / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies; D012907:Smoking; D014029:Tobacco Use Disorder / Q000235:genetics*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*; D044465:White People
chemical_list: D014446:Tyrosine 3-Monooxygenase