title: The role of TMPRSS6 polymorphisms in iron deficiency anemia partially responsive to oral iron treatment.
abstract: Iron refractory iron deficiency anemia (IRIDA) is a rare hereditary disease caused by mutations in TMPRSS6 gene encoding Matriptase-2, a negative regulator of hepcidin transcription. Up to now, 53 IRIDA patients from 35 families with different ethnic origins have been reported and 41 TMPRSS6 mutations have been identified. TMPRSS6 polymorphisms are more frequent than mutations, and have been associated with variation in iron and hematologic parameters. Our study evaluated their presence in 113 subjects with iron deficiency anemia (IDA) partially responsive to oral iron therapy and in 50 healthy blood donors. Thalassemic trait was diagnosed in 38 patients. Sequencing analysis of TMPRSS6 gene revealed that the frequency of several polymorphisms was markedly different between IDA subjects and controls. In particular, the V736A TMPRSS6 polymorphism was associated to moderately lower hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin levels, and in thalassemia carriers with marked anemia and microcytosis. A new variant-H448R- and two uncommon polymorphisms -A719T and V795I- were also identified. These results indicate that TMPRSS6 polymorphisms are more frequent in subjects with persistent IDA than in healthy controls, and in thalassemia carriers V736A variant may account for lower hemoglobin and MCV levels. Further studies in larger court of patients are necessary to identify potential haplotypes and polymorphisms responsible for low response to oral iron treatment and may be useful for planning a correct iron supplementation.
authors.affiliation: Dipartimento di Medicina Interna, IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Italy; Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Poggiali
authors.forename: Fabio
authors.initials: F
authors.lastname: Andreozzi
authors.forename: Isabella
authors.initials: I
authors.lastname: Nava
authors.forename: Dario
authors.initials: D
authors.lastname: Consonni
authors.forename: Giovanna
authors.initials: G
authors.lastname: Graziadei
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Cappellini
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy* / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005296:Ferrous Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D006397:Hematinics / Q000008:administration & dosage / Q000627:therapeutic use*; D006454:Hemoglobins / Q000032:analysis; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007501:Iron / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012697:Serine Endopeptidases / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005296:Ferrous Compounds; D006397:Hematinics; D006454:Hemoglobins; D008565:Membrane Proteins; C020748:ferrous sulfate; D007501:Iron; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human