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 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.
Keskitalo
Kaisu
K
Department of Public Health, University of Helsinki, Finland. kaisu.keskitalo@helsinki.fi
Broms
Ulla
U
Heliövaara
Markku
M
Ripatti
Samuli
S
Surakka
Ida
I
Perola
Markus
M
Pitkäniemi
Janne
J
Peltonen
Leena
L
Aromaa
Arpo
A
Kaprio
Jaakko
J
D000328:Adult; D000368:Aged; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D003367:Cotinine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D012907:Smoking / Q000097:blood / Q000235:genetics; D014029:Tobacco Use Disorder / Q000097:blood / Q000235:genetics*
D003367:Cotinine; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human; C447159:CHRNB4 protein, human