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. 2009 Oct 15;18(20):4007-12.
doi: 10.1093/hmg/ddp322. Epub 2009 Jul 23.

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

Kaisu Keskitalo  1 , Ulla Broms, Markku Heliövaara, Samuli Ripatti, Ida Surakka, Markus Perola, Janne Pitkäniemi, Leena Peltonen, Arpo Aromaa, Jaakko Kaprio
Affiliations

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

Kaisu Keskitalo et al. Hum Mol Genet. .

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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Figures

Figure 1.
Figure 1.
Relationship between number of cigarettes smoked daily (CPD) and immune-reactive serum cotinine levels with a lowess curve within daily smokers (n = 516).
Figure 2.
Figure 2.
Results of the association analysis for immune-reactive cotinine level (ng/ml) and number of cigarettes smoked per day (CPD).
Figure 3.
Figure 3.
Mean immune-reactive cotinine levels (ng/ml) and their standard errors corresponding to different genotypes of rs1051730 within daily smokers successfully genotyped (n = 515).
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