Analysis of ^Gγ-158(C→T) polymorphism in hemoglobin E/β-thalassemia major in Southern China

Hemoglobin E/β-thalassemia(HbE/β-thalassemia) is a common form of severe thalassemia syndromes in the Southern Chinese provinces[1]. Clinical manifestations of these patients range from nearly asymptomatic to severe β-thalassemia disease. The ^Gγ-158(C→T) polymorphism (- 158 Xmn I ^Gγ-globin polymorphism) has been shown to be associated with the increased production of HbF and can strongly influence this heterogeneity of HbE/β-thalassemia[1‐6]. The condition of the - 158 Xmn I ^Gγ-globin polymorphism has been rarely reported in HbE/β-thalassemia majors from Southern China. The present study was to investigate the frequency of the - 158 Xmn I ^Gγ-globin polymorphism and its association with high HbF level in HbE/β-thalassemia major patients of the Southern Chinese.

The clinical data were collected from 32 patients with HbE/β-thalassemia major who were seen at the First Affiliated Hospital, GuangXi Medical University. We also collected data from and compared with 30 unrelated healthy individuals. Table 1 shows the existence of the - 158 Xmn I ^Gγ-globin polymorphism among HbE/β-thalassemia major and healthy controls. The frequency of polymorphism in HbE/β-thalassemia major (65.63%) was significantly higher than those in healthy controls (P < 0.00). In these patients, there were 6 β-thalassemia mutations detected in trans to the βE-thalassemia mutation. None of α-thalassmeia and homozygote of the -158 Xmn I ^Gγ-globin polymorphism were found in all samples. Fig 1. displays the association between the -158 Xmn I ^Gγ-globin polymorphism and HbF level among the HbE/β-thalassemia major. The HbF level in Xmn I +/- group was more than that in Xmn I -/- group, confirming the significant difference between these two groups. The analysis by Spearman correlation indicated that the - 158 Xmn I ^Gγ-globin polymorphism was associated with increased HbF systhesis (r_p = 0.588).

In HbE/β-thalassemia, particularly in the major cases, during hematopoietic stress, point mutation at G-gamma promoter (the - 158 Xmn I ^Gγ-globin polymorphism) can induce high gamma chain production rate[7]. The heavy hematopoietic stress from severe anemia may thus leads to the high frequency of this polymorphism in Southern Chinese patients with HbE/β-thalassemia major. This is the first report of the frequency of the - 158 Xmn I ^Gγ-globin polymorphism in patients with HbE/β-thalassemia major in Southern China. These data suggest that screening of the - 158 Xmn I ^Gγ-globin polymorphism and HbF level in early childhood may help on the management of HbE/β-thalassemia major patients and possibly prevent severe complications in Southern China.