Literature DB >> 19628476

Association of serum cotinine level with a cluster of three nicotinic acetylcholine receptor genes (CHRNA3/CHRNA5/CHRNB4) on chromosome 15.

Kaisu Keskitalo1, Ulla Broms, Markku Heliövaara, Samuli Ripatti, Ida Surakka, Markus Perola, Janne Pitkäniemi, Leena Peltonen, Arpo Aromaa, Jaakko Kaprio.   

Abstract

A cluster of three nicotinic acetylcholine receptor genes on chromosome 15 (CHRNA5/CHRNA3/CHRNB4) has been shown to be associated with nicotine dependence and smoking quantity. The aim of this study was to clarify whether the variation at this locus regulates nicotine intake among smokers by using the level of a metabolite of nicotine, cotinine, as an outcome. The number of cigarettes smoked per day (CPD) and immune-reactive serum cotinine level were determined in 516 daily smokers (age 30-75 years, 303 males) from the population-based Health2000 study. Association of 21 SNPs from a 100 kb region of chromosome 15 with cotinine and CPD was examined. SNP rs1051730 showed the strongest association to both measures. However, this SNP accounted for nearly a five-fold larger proportion of variance in cotinine levels than in CPD (R(2) 4.3% versus 0.9%). The effect size of the SNP was 0.30 for cotinine level, whereas it was 0.13 for CPD. Variation at CHRNA5/CHRNA3/CHRNB4 cluster influences nicotine level, measured as cotinine, more strongly than smoking quantity, measured by CPD, and appears thus to be involved in regulation of nicotine levels among smokers.

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Year:  2009        PMID: 19628476      PMCID: PMC2748889          DOI: 10.1093/hmg/ddp322

Source DB:  PubMed          Journal:  Hum Mol Genet        ISSN: 0964-6906            Impact factor:   6.150


  19 in total

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  67 in total

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4.  Associations of nicotine intake measures with CHRN genes in Finnish smokers.

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Journal:  Nicotine Tob Res       Date:  2011-04-16       Impact factor: 4.244

5.  Association of the nicotine metabolite ratio and CHRNA5/CHRNA3 polymorphisms with smoking rate among treatment-seeking smokers.

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Review 8.  Nicotinic acetylcholine receptors and nicotine addiction: A brief introduction.

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