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  • GENERAL-POPULATION  (3)
  • 1
    Keywords: RECEPTOR ; Germany ; LUNG-CANCER ; COHORT ; DISEASE ; EPIDEMIOLOGY ; HISTORY ; POPULATION ; RISK ; GENE ; GENES ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; SUSCEPTIBILITY LOCUS ; DISTRIBUTIONS ; SUBUNIT ; smoking ; genetic polymorphism ; TOBACCO ; MAPS ; SINGLE ; ADULTS ; GENETIC EPIDEMIOLOGY ; VARIANT ; DEPENDENCE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SNPs ; GENOTYPE ; HAPLOTYPES ; USA ; smoking cessation ; GENOME-WIDE ASSOCIATION ; GENERAL-POPULATION ; ROBUST ; historical cohort study
    Abstract: Background: Evidence has recently accumulated that single nucleotide polymorphisms in the genetic region encoding the nicotinic acetylcholine receptor subunits alpha-5, alpha-3, and beta-4 are associated with smoking and nicotine dependence. We aimed to determine whether these genetic variations are also predictive of smoking cessation. Methods: Lifetime history of smoking was assessed by questionnaire at enrolment into a large epidemiological study of the German elderly population (ESTHER study). Cox proportional hazards modeling was applied in a retrospective cohort approach to determine the associations of individual polymorphisms and haplotypes with smoking cessation probability in 1446 subjects who reported regularly smoking more than 20 cigarettes at some point in their lives. Results: Given the genotype distributions and number of cessation events observed, the power to detect associations ranged from 54% to 97% for hazard ratios of 1.2 to 1.4 in case of the variant with strongest prior evidence (alpha = .05). Nonetheless, neither individual polymorphisms nor inferred multilocus haplotypes were significantly associated with smoking cessation. Conclusions: Although the robust association of the nicotinic acetylcholine receptor subunit genes investigated with smoking-related phenotypes is an apparent success story of genetic epidemiology, the respective variations seem to exert no relevant influence on smoking cessation probability in heavy smokers in the general population
    Type of Publication: Journal article published
    PubMed ID: 18996504
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  • 2
    Keywords: Germany ; MODEL ; MODELS ; COHORT ; EPIDEMIOLOGY ; POPULATION ; GENES ; PATIENT ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; VARIANTS ; CARE ; HEALTH ; genetics ; smoking ; REPLICATION ; TOBACCO ; SINGLE ; REGRESSION ; VARIANT ; DETERMINANTS ; DEPENDENCE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; CATECHOL-O-METHYLTRANSFERASE ; PHARMACOGENETICS ; GENOTYPE ; EVENTS ; pharmacology ; USA ; smoking cessation ; population-based ; biotechnology ; GENERAL-POPULATION ; NICOTINE DEPENDENCE ; COMT ; Genetic ; CONFIDENCE ; historical cohort study ; PROPORTION
    Abstract: Genome-wide studies have identified single nucleotide polymorphisms associated with smoking behaviour and nicotine dependence. Less is known about genetic determinants of smoking cessation, but rs4680 in COMT has recently been shown to explain a substantial proportion of the variation in cessation in the general population. We attempted to replicate the reported, clinically relevant effect in a population-based retrospective cohort analysis of 1443 ever-heavy smokers, of whom 925 had reached abstinence. In Cox regression models, neither rs4680 nor two polymorphisms nearby were associated with smoking cessation. The adjusted relative cessation rate (95 percent confidence interval) in rs4680 methionine carriers in reference to valine homozygotes was 0.97 (0.83-1.12). The absence of a significant effect of rs4680 in this statistically well-powered study - the 95% confidence interval even excluding the previously reported effect - highlights the need for rigorous replication efforts and suggests that rs4680 genotype should not yet be considered informative for smoking patient care. Pharmacogenetics and Genomics 19:657-659 (C) 2009 Wolters Kluwer Health / Lippincott Williams & Wilkins
    Type of Publication: Journal article published
    PubMed ID: 19584770
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  • 3
    Keywords: RECEPTOR ; Germany ; MODEL ; MODELS ; SUPPORT ; COHORT ; DISEASE ; EPIDEMIOLOGY ; POPULATION ; RISK ; GENE ; SAMPLE ; SAMPLES ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; score ; PHENOTYPES ; SUBUNIT ; genetics ; smoking ; REGION ; PHENOTYPE ; VARIANT ; DEPENDENCE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; ADDICTION ; SINGLE-NUCLEOTIDE POLYMORPHISMS ; pharmacogenomics ; pharmacology ; smoking cessation ; EXTENT ; Polymorphism,Single Nucleotide ; GENERAL-POPULATION ; genetic association ; NICOTINE DEPENDENCE ; Genetic ; Determination ; CHRNA4 ; Fagerstrom score ; TOBACCO DEPENDENCE
    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 (〈= 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. The Pharmacogenomics Journal (2009) 9, 219-224; doi: 10.1038/tpj.2009.6; published online 17 March 2009
    Type of Publication: Journal article published
    PubMed ID: 19290018
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