title: Severity differences in beta-thalassaemia/haemoglobin E syndromes: implication of genetic factors.
abstract: Genetic factors determining the difference in severity of anaemia in beta-thalassaemia/HbE disease were studied in 90 patients who had haemoglobin levels, at steady state, ranging from 4.2 to 12.6 g/dl. Co-inheritance of alpha-thalassaemia 2 and haemoglobin Constant Spring could significantly decrease the severity of the disease. Inheritance of a beta-thalassaemia chromosome with Xmn I cleavage site at position -158 of the G gamma-globin gene which was linked to the haplotype -+-++ or ++-++, was associated with a milder anaemia. Two copies of these alleles were necessary to produce a significant clinical effect. Increased expression of the G gamma-globin gene and higher production of haemoglobin F, which could reduce the overall globin chain imbalance, were also associated with homozygosity for the Xmn I cleavage site and thus with less severe anaemia. However, this effect was not seen in Xmn I site heterozygotes. Whether the effects of the Xmn I polymorphism, HbF concentration and G gamma/A gamma ratio act separately or through common mechanisms in reducing anaemia remains to be ascertained.
authors.affiliation: Department of Medicine, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand.
authors.forename: P
authors.initials: P
authors.lastname: Winichagoon
authors.forename: V
authors.initials: V
authors.lastname: Thonglairoam
authors.forename: S
authors.initials: S
authors.lastname: Fucharoen
authors.forename: P
authors.initials: P
authors.lastname: Wilairat
authors.forename: Y
authors.initials: Y
authors.lastname: Fukumaki
authors.forename: P
authors.initials: P
authors.lastname: Wasi
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D005319:Fetal Hemoglobin / Q000032:analysis; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006446:Hemoglobin E / Q000032:analysis*; D006801:Humans; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic; D017086:beta-Thalassemia / Q000097:blood / Q000235:genetics*
chemical_list: D005914:Globins; D006446:Hemoglobin E; D005319:Fetal Hemoglobin