Activity of cytochrome P450 1A2 in relation to hepatic iron accumulation in transfusion-dependent β-thalassaemia major patients

被引:2
作者
Shteyer, E. [1 ]
Nitzan, I. [1 ]
Godfarb, A. [2 ]
Hemed, N. [3 ]
Revel-Vilk, S. [4 ]
机构
[1] Hadassah Hebrew Univ Med Ctr, Pediat Gastroenterol Unit, IL-91200 Jerusalem, Israel
[2] Hadassah Hebrew Univ Med Ctr, Dept Hematol, IL-91200 Jerusalem, Israel
[3] Hadassah Hebrew Univ Med Ctr, Dept Med, Liver Unit, IL-91200 Jerusalem, Israel
[4] Hadassah Hebrew Univ Med Ctr, Pediat Hematol Oncol Dept, IL-91200 Jerusalem, Israel
关键词
C-13-methacetin breath test; blood transfusion; cytochrome P450 1A2; iron overload; -thalassaemia major; C-13-METHACETIN BREATH TEST; CYP1A2; GENE; UROPORPHYRIA; INFECTION; POLYMORPHISM; PHENOTYPE; ENZYMES; INJURY; MOUSE; MICE;
D O I
10.1111/vox.12223
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BackgroundCytochrome 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 -thalassaemia major. MethodsThe C-13-methacetin continuous breath test was performed on 30 consecutive patients with transfusion-dependent -thalassaemia major. CYP1A2 activity was measured by the rate at which the C-13 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). ResultsCytochrome P450 1A2 activity in patients with transfusion-dependent - 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*MRI63ms); adjusted odds ratio (OR; 95% CI) for hepatic iron accumulation in patients with low CYP1A2 activity was 0047 (0003-072; P=0021). 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. ConclusionActivity of CYP1A2 is associated with hepatic iron accumulation in patients with transfusion-depended -thalassaemia major. Further studies are needed to assess the exact role of CYP1A2 in iron metabolism in human.
引用
收藏
页码:268 / 273
页数:6
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