Nicotinic Acetylcholine Receptor Variants Are Related to Smoking Habits, but Not Directly to COPD

Genome-wide association studies identified single nucleotide polymorphisms (SNPs) in the nicotinic acetylcholine receptors (nAChRs) cluster as a risk factor for nicotine dependency and COPD. We investigated whether SNPs in the nAChR cluster are associated with smoking habits and lung function decline, and if these potential associations are independent of each other. The SNPs rs569207, rs1051730 and rs8034191 in the nAChR cluster were analyzed in the Vlagtwedde-Vlaardingen cohort (n = 1,390) that was followed for 25 years. We used GEE and LME models to analyze the associations of the SNPs with quitting or restarting smoking and with the annual FEV1 decline respectively. Individuals homozygote (CC) for rs569207 were more likely to quit smoking (OR (95%CI) = 1.58 (1.05–2.38)) compared to wild-type (TT) individuals. Individuals homozygote (TT) for rs1051730 were less likely to quit smoking (0.64 (0.42; 0.97)) compared to wild-type (CC) individuals. None of the SNPs was significantly associated with the annual FEV1 decline in smokers and ex-smokers. We show that SNPs in the nAChR region are associated with smoking habits such as quitting smoking, but have no significant effect on the annual FEV1 decline in smokers and ex-smokers, suggesting a potential role of these SNPs in COPD development via smoking habits rather than via direct effects on lung function

CYP2A6 genotypes and coumarin-oxidation phenotypes in a Thai population and their relationship to tobacco smoking

Objective: To investigate the association between polymorphisms in the human CYP2A6 gene, CYP2A6 enzyme activity and the influence of cigarette smoking in a Thai population. Methods: Coumarin (5 mg capsule) was administered to 194 healthy Thai subjects. Genetic variation of the CYP2A6 gene was identified using PCR methods. The excreted dose of 7-hydroxycoumarin (as a percentage of the urine concentration) 2 h after administration was calculated as an index of coumarin metabolism. Results: The frequencies of CYP2A6 alleles1A,1B,4C,7,8,9 and10 were 34.0, 35.3, 9.3, 6.4, 0.5, 12.1 and 2.4%, respectively. Of the 194 subjects tested, the number (percentages) of Thai participants classified as ultra-rapid, extensive, intermediate and poor metabolizers were 8 (4.1%), 159 (82.0%) 22 (11.3%) and five (2.6%), respectively. Conclusion: A relationship between the interindividual differences in coumarin metabolism and genetic polymorphisms of the CYP2A6 gene was observed

A influência da genética na dependência tabágica e o papel da farmacogenética no tratamento do tabagismo The influence of genetics on nicotine dependence and the role of pharmacogenetics in treating the smoking habit

Mesmo com os esforços intensivos para o controle do tabagismo nas últimas décadas, uma proporção substancial de pessoas inicia a fumar ou mantém-se fumando apesar do pleno conhecimento dos malefícios do hábito. Os estudos têm focado atualmente as bases genéticas da adição nicotínica. O tabagismo tem sido associado a vários polimorfismos genéticos, mas os fatores ambientais também devem ser enfatizados. Esta revisão apresenta alguns dos principais dados disponíveis dos estudos genéticos sobre o comportamento tabágico. Esta linha de pesquisa poderá, no futuro, ajudar os clínicos a individualizar o tipo, a dosagem e a duração do tratamento da dependência tabágica, conforme o genótipo de cada fumante, maximizando a eficácia do esquema proposto.<br>Despite the considerable efforts made in the fight against smoking in the last decades, there are still substantial numbers of people who, in full knowledge of the health hazards, begin smoking or continue smoking. Recent studies have focused on the genetic bases of the nicotine addiction. Various genetic polymorphisms have been associated with smoking. However, environmental factors have also been shown to play a role. In this review, we present some of the principal data collected in genetic studies of smoking behavior. The results obtained through this line of research will eventually aid clinicians in individualizing the type, dosage and duration of treatment for patients with nicotine dependence in accordance with the genotype of each smoker, thereby maximizing the efficacy of the proposed treatment regimen