Cytochrome P450 2E1 and Iron Overload

Cytochrome P450 2E1 and Iron Overload

The aim of the study is to determine, in patients presenting hepatic iron overload (genetic haemochtomatisis or dysmetabolic iron overload syndrome), the effects of venesection therapy on cytochrome P450 2E1 activity by comparing the rates of metabolization of chlorzoxazone before and after venesection.

Inclusion Criteria:

• Male patients aged from 18 to 70 years
• Hepatic iron overload measured by magnetic resonance imaging [MRI] (> 36 µmol/g and < 200 µmol/L)
• Homozygosity for the C282Y mutation of the HFE or dysmetabolic iron overload syndrome (DIOS) based on the presence of at least one of these following metabolic abnormalities:
• Overweight: BMI > 25 kg/m2
• Waist/hip circumference (cm) > 0.90
• Diabetes mellitus (fasting blood glucose level >1.25g/L or blood glucose level after 2 hours > 2g/L) or glucose intolerance (fasting blood glucose level between 1.10 and 1.25g/L)
• Total cholesterolemia > 6.2 mmol/L or HDL-Cholesterol < 0.9 mmol/L
• TG>= 1.7 mmol
• Written informed consent

Non-Inclusion Criteria:

• Consumption of alcohol > 50 g/day and of any CYP2E1 inhibitor substances
• Smoker > 5 cigarets/day
• History of blood donation or venesection
• Other causes of iron overload: aceruloplasminaemia, haematological disorder (abnormal blood counting), late cutaneous porphyria (cutaneous bullous disorders and photosensibilisation) , martial treatment, repeated transfusions.
• Inflammatory syndrome (CRP > 3ng/ml)