Analysis of the Genotypes in a Chinese Population with Increased Hb A₂ and Low Hematological Indices

Increased Hb A₂ is considered the most reliable hematological finding for the identification of β-thalassemia (β-thal) carriers. The aim of this study was to determine the underlying genetic factors associated with a high Hb A₂ level in a Chinese population. Subjects were recruited from couples preparing for pregnancy who participated in the thalassemia screening program during a 2-year period. DNA analyses were used for diagnosis of β-thal and other genetic factors. A total of 5985 adults who screened positive for β-thal were recruited. Of these, 5933 (99.1%) were detected to have a β-thal mutation. In the remaining 52 (0.9%) individuals without mutations involving the β-globin gene cluster, 16 were found to have Krüppel-like factor 1 (KLF1) gene variants, and two had an α-globin gene triplication. There were still 34 individuals with unknown genetic factors for their raised Hb A₂ values. The results of this study indicate that genetic factors other than β-thal can rarely contribute to the elevation of Hb A₂. These subjects usually have borderline microcytic red cell indices and Hb A₂ values.