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

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 t...

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Bibliographic Details
Published in:Human molecular genetics 2009-10, Vol.18 (20), p.4007-4012
Main Authors: Keskitalo, Kaisu, Broms, Ulla, Heliövaara, Markku, Ripatti, Samuli, Surakka, Ida, Perola, Markus, Pitkäniemi, Janne, Peltonen, Leena, Aromaa, Arpo, Kaprio, Jaakko
Format: Article
Language:English
Subjects:
Adult
Aged
Association Studies
Biological and medical sciences
Chromosomes, Human, Pair 15 - genetics
Cotinine - blood
Fundamental and applied biological sciences. Psychology
Genetics of eukaryotes. Biological and molecular evolution
Humans
Male
Middle Aged
Molecular and cellular biology
Nerve Tissue Proteins - genetics
Polymorphism, Single Nucleotide
Receptors, Nicotinic - genetics
Smoking - blood
Smoking - genetics
Tobacco Use Disorder - blood
Tobacco Use Disorder - genetics
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Summary: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 (R2 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.
ISSN:0964-6906
1460-2083
DOI:10.1093/hmg/ddp322