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

Abstract

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.

Keywords:

• α-Thalassemia (α-thal)
• β-thalassemia (β-thal)
• Hb A₂
• Krüppel-like factor 1 (KLF1) gene mutations
• screening

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was supported by grants from the NSFC/National Natural Science Foundation of China [81571448], the Guangdong Provincial Department of Science and Technology Agency [2016A020215218], and Health and Family Planning Commission of Guangdong Province [2016119153114316].