Association of CYP2A6 deletion polymorphism with smoking habit and development of pulmonary emphysema

Abstract

Background: Nicotine is responsible for smoking dependence and is mainly metabolised by CYP2A6. Several types of genetic polymorphism of CYP2A6 have been reported, but their relation to smoking habit and chronic obstructive pulmonary disease (COPD) phenotypes has not been fully clarified. Methods: 203 current or ex-smokers (lifelong cigarette consumption (CC) >10 pack years) with subclinical and established COPD phenotypes were clinically evaluated and pulmonary function tests and a chest CT scan were performed (smoker group). The non-smoker group consisted of 123 healthy volunteers. CYP2A6 genotypes were determined in both groups. Results: The percentage of subjects with a CYP2A6del allele (genotype D) was lower in heavy smokers (20.5%, n=88, CC >60 pack years) than in light smokers (37.4%, n=115, CC 10-59 pack years, χ

Impact of CYP2A6 genotype on pretreatment smoking behaviour and nicotine levels from and usage of nicotine replacement therapy

“…CYP2A6 slow metabolizers smoked fewer cigarettes per day than normal metabolizers (Figure 2), consistent with several studies in adults 8,12,14,15,17 and one study in adolescents. 22 The effect of CYP2A6 genotype on cigarette consumption was observed here among treatment-seeking smokers, whose characteristics and smoking behaviours tend to be different from those of the general smoking population.…”

“…This may explain the lower CYP2A6*4 allele frequency reported here (Table 1) compared to a general smoking population. 15 The CYP2A6*4 allele has been associated with lower risk for being a smoker, reduced cigarette consumption and reduced risk for lung disease, [12][13][14]17 and thus it may be under-represented among treatment-seeking smokers, as participants in this study were long duration heavier smokers with a mean smoking duration of 30 years. In addition, among slow metabolizers in this treatment-seeking population, there was a greater percentage of women and those with fewer years of education compared to normal metabolizers.…”

“…9,10 Variability in the rate of nicotine metabolism owing to CYP2A6 genetic polymorphisms may also influence nicotine plasma levels, 6,8,11 and a number of studies in adults have demonstrated that CYP2A6 genetic variation, causing reduced or absent enzyme activity, is associated with a reduced risk of being a smoker, lower amount smoked, altered smoking intensity and increased quitting. 8,[12][13][14][15][16][17] However, not all studies provide consistent results. [18][19][20] Investigations of the impact of CYP2A6 genotype on smoking behaviours usually recruit participants from the general smoking population or from cancer and health institutes.…”

“…[18][19][20] Investigations of the impact of CYP2A6 genotype on smoking behaviours usually recruit participants from the general smoking population or from cancer and health institutes. 12,14,15,17,21,22 Smokers who seek treatment, compared to the general smoking population, are more often heavier smokers, have higher Fagerstrom Test for Nicotine Dependence (FTND) scores, indicating greater nicotine dependence, and are more likely to be women, older in age and have higher levels of education. 23,24 In addition, smokers enrolled in cessation studies may differ from the general smoking population owing to the eligibility criteria (e.g.…”

CYP2A6 polymorphisms are associated with nicotine dependence and influence withdrawal symptoms in smoking cessation

“…[8][9][10] Next, the amounts of daily nicotine intake were also examined. As shown in Figure 1b, CYP2A6 genotype is likely to be linked with daily nicotine intake, proposing the possible association between CYP2A6 genotypes and nicotine dependence.…”