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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 13C-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 13C 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. Conclusion 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. [ABSTRACT FROM AUTHOR]