Molecular characterisation of genes involved in iron homeostasis

Abstract

This is the first study to have performed comprehensive analysis of genes involved in iron metabolism in diverse conditions of iron deficiency and iron overload. This study essentially helped us to understand and review the concept of iron deficiency anemia beyond nutritional deficiency. The significant association of genetic variants with ferritin levels in iron eficiency anemia highlights this notion. We were able to identify mutations in seven patients with atypical anemia and this is the first report from India addressing the genetic basis of iron deficiency anemia providing an early diagnosis and management of patients with unexplained anemia. We have designed an algorithm to easily identify atypical causes of anemia. This is the first report demonstrating the role of genetic variants in determining not only the basal iron status but also the response to iron supplements in pregnancy. For the first time in India we have identified mutations in HFE and HFE2 gene in patients with hemochromatosis. Beta thalassemia is a heterogeneous entity in many aspects and our study indicates that variants in genes controlling hepcidin and GDF15 have potential impact in determining the body iron stores. The analysis of gene regulation in erythroid and placental compartment under iron deficient condition rendered an insight into iron metabolism and projected a probable role of GDF15 in iron homeostasis. Our data highlights deregulated expression of iron genes in beta thalassemia during ineffective erythropoiesis likely contributing to its pathogenesis. The present study helped us to define a role of p53 in GDF15 induction and implicates its probable role in apoptosis and ineffective erythropoiesis. newline