Glutathione S-Transferase Gene Polymorphism and Heart Iron Overload in Thalassemia Major.

Heart is the target lethal organ for iron accumulation in thalassemia major. Currently, magnetic resonance imaging (MRI) is the only non-invasive method with the potential to assess myocardial iron. MRI T2* has proven to be a fast, simple, robust and clinically useful tool for the assessment of cardiac iron load. In chelated patients, myocardial iron is usually inversely related to compliance with chelation while there is no meaningful correlation with liver iron and serum ferritin concentration measured at the time of T2* assessment. However, in a subset of patients, myocardial iron overload occurs despite an history of good compliance with chelation therapy, suggesting the possible role of genetic factors. Several gene polymorhisms including apolipoprotein epsylon and HLA haplotypes have been described as protective or predisposing factors for cardiac iron dysfunction. Wu et al. (2006) analyzed polymorphisms of two endogenous antioxidant enzymes, glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1). They found that the GSTM1 null (deleted) genotype was associated with a decreased signal intensity ratio on MRI, suggesting that genetic variations of the GSTM1 enzyme are associated with cardiac iron deposition. The aim of the current study was to evaluate if the GSTM1 null genotype is a predisposing factor for myocardial iron overload in thalassemia major patients on chelation treatment with desferrioxamine with low body iron load as assessed by serum ferritin levels. Allelic distribution of wild and null GSTM1 genotype was assessed in 24 patients with thalassemia major in whom the severe myocardial iron overload (T2*