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Breitling, L.P.* ; Dahmen, N.* ; Mittelstraß, K. ; Rujescu, D.* ; Gallinat, J.* ; Fehr, C.* ; Giegling, I.* ; Lamina, C. ; Illig, T. ; Müller, H.* ; Raum, E.* ; Rothenbacher, D.* ; Wichmann, H.-E. ; Brenner, H.* ; Winterer, G.*

Association of nicotinic acetylcholine receptor subunit α4 polymorphisms with nicotine dependence in 5500 Germans.

Pharmacogenomics J. 9, 219-224 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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 (<= 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords smoking; Fagerstrom score; polymorphism; single nucleotide; smoking cessation; CHRNA4; epidemiology; tobacco dependence; gene; smoking; disease; chrna4; addiction; cohort; risk
ISSN (print) / ISBN 1470-269X
e-ISSN 1473-1150
Journal Pharmacogenomics Journal, The
Quellenangaben Volume: 9, Issue: 4, Pages: 219-224 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)