Role of TfR2-Y250X and TfR1- rs3817672 Single Nucleotide Polymorphism on Pathophysiology of Iron Deficiency Anemia

摘要

Background: Transferrin receptor (TfR) is a carrier protein for transferrin. It isregulated in response to intracellular iron concentration and plays a role forthe import of iron into the cell. The transferring receptor 2 (TFR2) gene showedhomology to transferrin receptor 1 (TFR1) gene and encodes a transmembraneprotein with a large extracellular domain, which is able to bind transferrin.Mutations in transferrin receptors (TfR2 and TfR1) may alter the pathophysiologyof iron deficiency anemia. Alteration in genes encoding transferring receptorcause change in iron homeostatsis and provides a tool for investigating theexcess iron absorption and abnormal iron distribution in iron related disorders.However the clinical significance of the interaction of transferring mutationswith iron deficiency anemia remains unclear. Thus, the objective of my studywas to investigate the effect of TFR1 and TFR2 genotypes on pathophysiologyof iron deficiency anemia.Study Design: Study subjects were 460 iron deficiency anemia patients and500 age and sex-matched healthy controls. Transferrin receptor, ferritin and CRPanalysis was done by ELISA method while ESR analysis was done according toWintrobes’s method. CBC analysis was done by auto–analyzer. TFR1-rs3817672SNP and TFR2 (Y250X) mutation was analyzed by using PCR RFLP method.Result: Amongst the iron deficiency anemia patients, 13 were heterozygous andfive were homozygous for rs3817672 SNP. TFR2 (Y250X) mutation was detected in6 patients with heterozygous conditions. None of the patients were presentinghomozygous condition while four controls were presenting heterozygous andone with homozygous condition. Controls were presenting 3% and 0.6% of TFR1rs3817672 SNP heterozygosity respectively.Conclusion: TfR2 -Y250X and TfR1-rs3817672 SNP showed clinical association withiron deficiency anemia and screening for mutations of TFR2 is a new diagnostictool that can be offered to patients who do not have HFE mutations or who haveincomplete HFE genotypes. This results may have practical implications for themolecular diagnosis of hemochromatosis. Genotyping the TFR gene should beincluded in the disease diagnostic protocols.