Alpha globin gene numbers: an important modifier of HbE/β thalassemia

Abstract

HbE [β 26 Glu-Lys] is the second most common abnormal Hb in humans. HbE when associated with β thalassemia (HbE/β thalassemia) in compound heterozygous state results in a clinically severe condition. HbE/β thalassemia has a very variable clinical phenotype. One of the possible explanations for the observed variable clinical severity is variation of α gene number. The main aims of this study were to determine the frequency of α deletion/mutations and triplication in HbE/β thalassemia patients and to study the effect of α gene numbers on the phenotype of these patients. 240 HbE/β thalassemia patients who attended the Hematology Outpatient Department of the Institute were studied. Patients were divided into three groups mild (score=0–3·5), moderate (score=4–7) and severe (score=7·5–10). α deletion was found in 22 (7·5%), out of these 22 patients 16 (11 αα/-α3·7, 4–α3·7/-α3·7 & 1 αα/--SA) were from Gp I and 6 (αα/-α3·7) were from Gp II. α triplication was found in 7 (2·9%) and out of these 7 patients 5 were (αα/αααanti-3·7) from Gp III and 2 were (αα/αααanti-3·7) from Gp II. The most common interaction was found to be HbE/β thalassemia and deletional α+-thalassemia (αα/-α3·7) followed by others. α deletions and point mutations genotype were mostly observed in the individuals from Gp I while α triplication was most frequent in Gp III individuals. Interaction of HbE/β thal with α-thalassemia is common in the Indian population. Patients inheriting α deletions and point mutations behaved mildly with some exceptions, while patients with α triplication had a severe phenotype requiring frequent transfusions.