Association of genes coding for the alpha-4, alpha-5, beta-2 and beta-3 subunits of nicotinic receptors with cigarette smoking and nicotine dependence.
We assessed whether smoking behavior was associated with nine polymorphisms in genes coding for the nicotinic receptor subunits alpha-4 (rs1044394, rs1044396, rs2236196 and rs2273504), alpha-5 (rs16969968), beta-2 (rs2072661 and rs4845378) and beta-3 (rs4953 and rs6474413).We conducted an Internet survey and collected saliva by mail for DNA and cotinine analyses, in Switzerland in 2003. We conducted DNA analyses for 277 participants and cotinine analyses for 141 current daily smokers. Cotinine levels were higher in carriers of the CC genotype of CHRNA4 rs1044396 (371 ng/ml) than in those with the CT or TT genotypes (275 ng/ml, p=0.049), a difference of 0.53 standard deviation units. However, this difference was not robust to correction for multiple testing using Bonferroni adjustment. These 9 polymorphisms were not otherwise associated with smoking behavior and nicotine dependence. There were possible associations between the temperament trait novelty seeking and CHRNA4 rs1044396, CHRNA5 rs16969968 and CHRNB2 rs4845378, but these associations were not robust to correction for multiple testing. We conclude that the analysis of polymorphisms in genes coding for four nicotinic acetylcholine receptor subunits (CHRNA4, CHRNA5, CHRNB2 and CHRNB3) and several smoking-related phenotypes revealed no statistically significant association.
Etter
Jean-François
JF
Institute of Social and Preventive Medicine, Faculty of Medicine, University of Geneva, CMU, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland. jean-francois.etter@unige.ch
Hoda
Jean-Charles
JC
Perroud
Nader
N
Munafò
Marcus
M
Buresi
Catherine
C
Duret
Claudette
C
Neidhart
Elisabeth
E
Malafosse
Alain
A
Bertrand
Daniel
D
D000328:Adult; D003367:Cotinine / Q000032:analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011978:Receptors, Nicotinic / Q000235:genetics*; D012463:Saliva / Q000737:chemistry; D012907:Smoking / Q000235:genetics* / Q000378:metabolism; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000378:metabolism
D003367:Cotinine; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; C447158:CHRNA5 protein, human; C539371:CHRNB3 protein, human