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Pharmacogenomics J. 2009 Aug;9(4):219-24. doi: 10.1038/tpj.2009.6. Epub 2009 Mar 17.

Association of nicotinic acetylcholine receptor subunit alpha 4 polymorphisms with nicotine dependence in 5500 Germans.

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  • 1Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany. L.Breitling@dkfz.de

Abstract

Polymorphisms in the CHRNA4 gene coding the nicotinic acetylcholine receptor subunit alpha 4 have recently been suggested to play a role in the determination of smoking-related phenotypes. To examine this hypothesis, we conducted a genetic association study in three large samples from the German general population (N(1)=1412; N(2)=1855; N(3)=2294). Five single-nucleotide polymorphisms in CHRNA4 were genotyped in 5561 participants, including 2707 heavily smoking cases (regularly smoking at least 20 cigarettes per day) and 2399 never-smoking controls (<or=100 cigarettes over lifetime). We examined associations of the polymorphisms with smoking case-control status and with the extent of nicotine dependence as measured by the Fagerstrom test of nicotine dependence (FTND) score (N=1030). The most significant association was observed between rs2236196 and FTND (P=0.0023), whereas the closely linked rs1044396 had most statistical support in the case-control models (P=0.0080). The consistent effect estimates across three independent cohorts elaborate on recently published functional studies of rs2236196 from the CHRNA4 3'-untranslated region and seem to converge with accumulating evidence to firmly implicate the variant G allele of this polymorphism in the intensification of nicotine dependence.

PMID:
19290018
[PubMed - indexed for MEDLINE]
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