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Association of CYP2A6 deletion polymorphism with smoking habit and development of pulmonary emphysema
  1. N Minematsu,
  2. H Nakamura,
  3. M Iwata,
  4. H Tateno,
  5. T Nakajima,
  6. S Takahashi,
  7. S Fujishima,
  8. K Yamaguchi
  1. Department of Medicine, School of Medicine, Keio University, Tokyo, Japan
  1. Correspondence to:
    Dr H Nakamura, Cardiopulmonary Division, Department of Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan;


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, χ2=6.8, p=0.01) or non-smokers (36.1%, n=122, χ2=6.0, p=0.01); lower in ex-smokers (20.7%, n=111) than in current smokers (41.3%, n=92, χ2=10.1, p<0.01); and lower in smokers with a high LAA (low attenuation area) score on the chest CT scan (18.4%, n=76, LAA ≥8.0) than in those with a low LAA score (37.0%, n=127, LAA <8.0, χ2=7.8, p<0.01).

Conclusions: Subjects with the CYP2A6del allele tend not to be heavy habitual smokers but can be light habitual smokers. The CYP2A6del polymorphism may inhibit smokers from giving up smoking, but appears to function as a protective factor against the development of pulmonary emphysema independent of smoking habit.

  • CYP2A6
  • genetic polymorphism
  • chronic obstructive pulmonary disease
  • smoking
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