Associations of nicotine intake measures with CHRN genes in Finnish smokers.
Nicotine Tob Res
; 13(8): 686-90, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21498873
ABSTRACT
INTRODUCTION:
Genetic effects contribute to individual differences in smoking behavior. Persistence to smoke despite known harmful health effects is mostly driven by nicotine addiction. As the physiological effects of nicotine are mediated by nicotinic acetylcholine receptors (nAChRs), we aimed at examining whether single nucleotide polymorphisms (SNPs) residing in nAChR subunit (CHRN) genes, other than CHRNA3/CHRNA5/CHRNB4 gene cluster previously showing association in our sample, are associated with smoking quantity or serum cotinine levels.METHODS:
The study sample consisted of 485 Finnish adult daily smokers (age 30-75 years, 59% men) assessed for the number of cigarettes smoked per day (CPD) and serum cotinine level. We first studied SNPs residing on selected nAChR subunit genes (CHRNA2, CHRNA4, CHRNA6/CHRNB3, CHRNA7, CHRNA9, CHRNA10, CHRNB2, CHRNG/CHRND) genotyped within a genome-wide association study for single SNP and multiple SNP associations by ordinal regression. Next, we explored individual haplotype associations using sliding window technique.RESULTS:
At one of the 8 loci studied, CHRNG/CHRND (chr2), single SNP (rs1190452), multiple SNP, and 2-SNP haplotype analyses (SNPs rs4973539-rs1190452) all showed statistically significant association with cotinine level. The median cotinine levels varied between the 2-SNP haplotypes from 220 ng/ml (AA haplotype) to 249 ng/ml (AG haplotype). We did not observe significant associations with CPD.CONCLUSIONS:
These results provide further evidence that the γ-δ nAChR subunit gene region is associated with cotinine levels but not with the number of CPD, illustrating the usefulness of biomarkers in genetic analyses.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Tabagismo
/
Fumar
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Receptores Nicotínicos
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Predisposição Genética para Doença
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Polimorfismo de Nucleotídeo Único
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Frequência do Gene
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
Nicotine Tob Res
Assunto da revista:
SAUDE PUBLICA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Finlândia