title: Alpha hemoglobin stabilizing protein: Its causal relationship with the severity of beta thalassemia.
abstract: Thalassemia major is characterized by anemia, iron overload and cellular damage. The severity of symptoms correlates with the alpha/non-alpha globin imbalance and is proportional to the magnitude of alpha chain excess. Alpha hemoglobin stabilizing protein (AHSP), the erythroid specific alpha globin chaperone, stabilizes free alpha chains, and prevents the formation of reactive oxygen radicals. Though AHSP expression has been linked to the severity of beta thalassemia, its role as a probable genetic modifier of disease severity, has still not been unequivocally established. In the present study, the level of the chaperone has been seen to vary in regularly transfused beta thalassemia patients, being underexpressed in 64% of cases, upregulated in 16% and comparable to controls in 20% of the cases. This discrepancy may be attributed to the degree of DNA damage, % HbF, and the number of nucleated RBCs in the peripheral blood of these patients. Results reveal that a decrease in the free alpha chain pool, and hence the repertoire of unbound iron, due to elevated HbF and/or the presence of nucleated RBCs in the peripheral blood results in the upregulation of the AHSP gene.
authors.affiliation: School of Studies in Biochemistry, Jiwaji University, Gwalior, India.
authors.forename: Chandan S
authors.initials: CS
authors.lastname: Sagar
authors.affiliation: School of Studies in Biochemistry, Jiwaji University, Gwalior, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Blood Bank, Jaya Arogya Hospital, Gajra Raja Medical College, Gwalior, India.
authors.forename: Dharmesh C
authors.initials: DC
authors.lastname: Sharma
authors.affiliation: School of Studies in Biochemistry, Jiwaji University, Gwalior, India. Electronic address: poornima1kishore@yahoo.com.
authors.forename: Purnima
authors.initials: P
authors.lastname: Kishor
mesh_terms: D000293:Adolescent; D001798:Blood Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004249:DNA Damage; D005260:Female; D005319:Fetal Hemoglobin / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008297:Male; D018832:Molecular Chaperones / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding; D012156:Reticulocytes; D012720:Severity of Illness Index; D055815:Young Adult; D055542:alpha-Globins / Q000378:metabolism*; D055544:beta-Globins / Q000235:genetics; D017086:beta-Thalassemia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism*
chemical_list: C468768:AHSP protein, human; D001798:Blood Proteins; D018832:Molecular Chaperones; D055542:alpha-Globins; D055544:beta-Globins; D005319:Fetal Hemoglobin
keywords: AHSP; Alpha chain toxicity; Beta thalassemia; DNA damage; HbF; Nucleated RBC