Iron dysregulation in beta-thalassemia

Iron deficiency anemia and iron overload conditions affect more than one billion people worldwide.Iron homeostasis involves the regulation of cells that export iron into the plasma and cells that utilize or store iron.The cellular iron balance in humans is primarily mediated by the hepcidin-ferroportin axis.Ferroportin is the sole cellular iron export protein,and its expression is regulated transcriptionally,post-transcriptionally and posttranslationally.Hepcidin,a hormone produced by liver cells,post-translationally regulates ferroportin expression on iron exporting cells by binding with ferroportin and promoting its internalization by endocytosis and subsequent degradation by lysosomes.Dysregulation of iron homeostasis leading to iron deposition in vital organs is the main cause of death in betathalassemia patients.Beta-thalassemia patients show marked hepcidin suppression,ineffective eiythropoiesis,anemia and iron overload.Beta-thalassemia is common in the Mediterranean region,Southeast Asia and the Indian subcontinent,and the focus of this review is to provide an update on the factors mediating hepcidin related iron dysregulation in beta-thalassemia disease.Understanding this process may pave the way for new treatments to ameliorate iron overloading and improve the long term prognosis of these patients.

Endogamous marriage and the prevalence of hemoglobin E in ethnic groups of northern Thailand

Objective:To investigate the impact of the endogamous marriage culture on the prevalence of the hemoglobin E(HbE) recessive variant.Methods:The prevalence of the hemoglobin E(HbE)recessive variant was determined by dot-blot hybridization in 4 endogamous villages(1 Mlabri and 3 Htin ethnic groups) in comparison with 9 other nearby non-endogamous populations.Results:Although the overall HbE prevalence in the population studied(8.44%,33/391)was not significantly different from that of the general southeast Asian population,a high prevalence and individuals with homozygous HbE were observed in two villages,the Mlabri from Wiang Sa district and the Htin from Thung Chang district of Nan province(26.3%and26.9%,respectively).The low HbE allelic frequency noticed in some endogamous populations suggests that not only endogamy but also other evolutionary forces,such as founder effect and HbE/β-thalassemia negative selection may have an effect on the distribution of the HbE trait.Conclusion:Our study strongly documents that cultural impact has to be considered in the extensive prevalence studies for genetic disorders in the ethnic groups of northern Thailand.