Nicotine dependence in a prospective population-based study of adolescents: The protective role of a functional tyrosine hydroxylase polymorphism
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2004-02-01
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Pharmacogenetics and Genomics
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LIPPINCOTT WILLIAMS & WILKINS
Melbourne Authors
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Melbourne Medical School
Paediatrics (RCH)
Melbourne School of Psychological Sciences
Paediatrics (RCH)
Melbourne School of Psychological Sciences
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Journal Article
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Anney, R. J. L., Olsson, C. A., Lotfi-Miri, M., Patton, G. C. & Williamson, R. (2004). Nicotine dependence in a prospective population-based study of adolescents: The protective role of a functional tyrosine hydroxylase polymorphism. Pharmacogenetics, 14 (2), pp.73-81. https://doi.org/10.1097/00008571-200402000-00001.
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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.