Possible association between reactive oxygen metabolites and karyotypic abnormalities in myelodysplastic syndromes.

594 haematologica/journal of hematology vol. 88(05):may 2003 Subjects homozygous for C282Y or Y250X were significantly younger (36.5 and 34.0 years vs 47.5 and 54.0, respectively, p <0.001) and had significantly higher ferritin levels and tranferrin saturation (1134.5 μg/L [range 68-3823 μg/L], 70.4% [range 12.6-96%] for individuals homozygous for C282Y and 900.0 μg/L [range 649-1151 μg/L], 90.0% [range 81.3-98.6%] for individuals homozygous for Y250X vs 597.6 μg/L [range 92737 μg/L], 46.2% [range 2.8-94.0%] for individuals with other mutations, p <0.001) than those showing other mutations. We did not find any difference in the frequency of HH gene mutations in the two groups of patients who were screened for 2 (82/148, 55.4%) or 12 (102/191, 53.4%) mutations; in fact, the analysis of 12 HH mutations identified only 4 HH gene mutations (C282Y, H63D, S65C in the HFE gene and Y250X in TfR2 gene) in our population, selected for having an abnormal iron status. This evidence raises the question about the utility and costs of this kind of screening in the general population. As regards the 151 subjects lacking HH mutations, in most cases (86.8%) iron overload was associated with other diseases, such as hepatitis C virus infection, alcoholism or systemic diseases which are known to have a role in iron accumulation. Although we did not find any correlation between the presence of liver diseases or solid cancers and HH gene mutations, we observed a high frequency of β-thalassemic trait in heterozygous subjects for H63D mutation (7/97, 7.2%). Increased iron turnover can be easily explained in patients with intermediate thalassemia because of the presence of chronic hemolysis, but is more difficult to explain in β-thalassemia gene carriers, unless it is assumed that H63D mutation may have a modulating effect on iron absorption in these subjects.7,8 In conclusion, our data confirm the high frequency (55.5%) of HH gene mutations in subjects with abnormal iron status.