title: Relationship between CYP2A6 genetic polymorphism, as a marker of nicotine metabolism, and ulcerative colitis.
abstract: BACKGROUND
  Ulcerative colitis (UC) is a common and difficult-to-treat disease. In non-smokers the relative risk of developing UC is 2.9 compared with smokers, who tend to have a later onset and a milder disease. Nicotine is the component of cigarette smoke responsible for the favorable effects in UC. Nicotine is metabolized by the enzyme CYP2A6. Subjects who are homozygotes for CYP2A6*4 gene polymorphism are poor nicotine metabolizers, while homozygotes for CYP2A6*1A polymorphism are extensive metabolizers.
  
  
  OBJECTIVE
  To compare the frequency of CYP2A6 and CHRNA3 polymorphisms among smokers and non-smokers with UC, and their effect on disease severity.
  
  
  METHODS
  Data on the age at onset of disease, disease activity, and treatment were obtained from questionnaires completed by the 69 subjects in our study group. CYP2A6 *1A,*4A and CHRNA3 polymorphisms were determined by polymerase chain reaction and restriction enzyme analysis.
  
  
  RESULTS
  Nine percent of the patients were current smokers, 30% were former smokers and 61% non-smokers. Among smokers and former smokers 63% were homozygotes for CYP2A6*1A and 4% were homozygotes for CYP2A6*4A, whereas among non-smokers 66% were homozygotes for CYP2A6*4A (P < 0.0001). There was no significant effect of CYP2A6 or CHRNA3 genotype on UC activity.
  
  
  CONCLUSIONS
  We found a very high proportion of poor nicotine metabolizers among non-smoking patients with UC and a very low proportion among current and former smokers, making it difficult to determine the effect of poor metabolizer genotype on disease activity in smokers with UC. However, it may be possible to identify UC patients who are poor metabolizers of nicotine and who may benefit from nicotine or nicotine-like pharmacological treatment.
authors: Medical Genetics Unit, Shaare Zedek Medical Center, Jerusalem, Israel.
authors: Gheona
authors: G
authors: Altarescu
authors: Daniel
authors: D
authors: Rachmilewitz
authors: Shoshana
authors: S
authors: Zevin
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D015897:Comorbidity; D065637:Cytochrome P-450 CYP2A6; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D009538:Nicotine / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000235:genetics*; D012720:Severity of Illness Index; D012907:Smoking / Q000235:genetics; D055815:Young Adult
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; D009538:Nicotine; D011978:Receptors, Nicotinic; C585710:CYP2A6 protein, human