title: Activity of cytochrome P450 1A2 in relation to hepatic iron accumulation in transfusion-dependent β-thalassaemia major patients.
abstract: BACKGROUND
  Cytochrome P450 1A2 (CYP1A2) is a cytochrome enzyme with a pivotal role in hepatic drug metabolism. Data from CYP1A2((-/-)) mouse suggest that CYP1A2 plays a role in aspects of hepatic iron toxicity. The aim of this study was to assess the activity of CYP1A2 in relation to hepatic iron load in patients with transfusion-dependent β-thalassaemia major.
  
  
  METHODS
  The (13) C-methacetin continuous breath test was performed on 30 consecutive patients with transfusion-dependent β-thalassaemia major. CYP1A2 activity was measured by the rate at which the (13) C substrate is metabolized and exhaled expressed as percentage dose recovery (PDR) per hour. CYP1A2 activity was correlated with clinical and laboratory parameters and hepatic iron accumulation by T2* magnetic resonance imaging (T2*MRI).
  
  
  RESULTS
  Cytochrome P450 1A2 activity in patients with transfusion-dependent β- thalassaemia major was positivity correlated with plasma ferritin levels. No correlation was found with age, duration and amount of red blood cell transfusion and type of iron chelation therapy. Low CYP1A2 activity was negatively associated with hepatic iron accumulation (T2*MRI ≤ 6.3 ms); adjusted odds ratio (OR; 95% CI) for hepatic iron accumulation in patients with low CYP1A2 activity was 0.047 (0.003-0.72; P = 0.021). Of the six patients with decreased activity of CYP1A2, five had no hepatic iron accumulation and one had mild hepatic iron accumulation by T2*MRI.
  
  
  CONCLUSIONS
  Activity of CYP1A2 is associated with hepatic iron accumulation in patients with transfusion-depended β-thalassaemia major. Further studies are needed to assess the exact role of CYP1A2 in iron metabolism in human.
authors.affiliation: Pediatric Gastroenterology Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Shteyer
authors.forename: I
authors.initials: I
authors.lastname: Nitzan
authors.forename: A
authors.initials: A
authors.lastname: Godfarb
authors.forename: N
authors.initials: N
authors.lastname: Hemed
authors.forename: S
authors.initials: S
authors.lastname: Revel-Vilk
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D019190:Iron Overload / Q000209:etiology / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D065227:Transfusion Reaction; D017086:beta-Thalassemia / Q000209:etiology / Q000378:metabolism*
chemical_list: D019388:Cytochrome P-450 CYP1A2
keywords: 13C-methacetin breath test; blood transfusion; cytochrome P450 1A2; iron overload; β-thalassaemia major