0000000000408573
AUTHOR
Elke Raum
Association of nicotinic acetylcholine receptor subunit alpha 4 polymorphisms with nicotine dependence in 5500 Germans.
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 nicotin…
Dopamine-related genes and spontaneous smoking cessation in ever-heavy smokers
Several studies have provided evidence for associations of polymorphisms located in and near dopamine-related genes and nicotine dependence and other smoking-related phenotypes, including pharmacogenetic interactions. Aim: The purpose of the present work was to examine the association of SNPs in the DOPA decarboxylase (DDC), dopamine receptor D2 (DRD2) and dopamine transporter (SLC6A3) genes with smoking cessation in a large retrospective study featuring approximately 900 cessation events. Materials & methods: Data originated from the enrollment questionnaire of the epidemiological ESTHER study of community-dwelling adults aged 50–74 years, conducted in the German state of Saarland bet…
Variants in COMT and spontaneous smoking cessation: retrospective cohort analysis of 925 cessation events
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% confidence interval) in rs4680 methion…
Smoking cessation and variations in nicotinic acetylcholine receptor subunits alpha-5, alpha-3, and beta-4 genes.
Background Evidence has recently accumulated that single nucleotide polymorphisms in the genetic region encoding the nicotinic acetylcholine receptor subunits α-5, α-3, and β-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…
Risk gene variants for nicotine dependence in the CHRNA5-CHRNA3-CHRNB4 cluster are associated with cognitive performance
Recent studies strongly support an association of the nicotinic acetylcholine receptor gene cluster CHRNA5-CHRNA3-CHRNB4 with nicotine dependence (ND). However, the precise genotype-phenotype relationship is still unknown. Clinical and epidemiological data on smoking behavior raise the possibility that the relevant gene variants may indirectly contribute to the development of ND by affecting cognitive performance in some smokers who consume nicotine for reasons of "cognition enhancement." Here, we tested seven single nucleotide polymorphisms (SNPs) rs684513, rs637137, rs16969968, rs578776, rs1051730, rs3743078, rs3813567 from the CHRNA5-CHRNA3-CHRNB4 gene cluster for association with ND, me…
Association of a variant in the muscarinic acetylcholine receptor 2 gene (CHRM2 ) with nicotine addiction
Genetic factors contribute to the overall risk of developing nicotine addiction, which is the major cause of preventable deaths in western countries. However, knowledge regarding specific polymorphisms influencing smoking phenotypes remains scarce. In the present study we provide evidence that a common single nucleotide polymorphism (SNP) in the 5′ untranslated region of CHRM2, the gene coding for the muscarinic acetylcholine receptor 2 is associated with nicotine addiction. CHRM2 was defined as a candidate gene for nicotine addiction based on previous evidence that linked variations in CHRM2 to alcohol and drug dependence. A total of more than 5,500 subjects representative of the German po…