A Novel Variant with Positive Natural Selection Influenced Hb A₂ Levels in Chinese Individuals with β-Thalassemia

Abstract

β-Thalassemia (β-thal) is the most common inherited hemolytic anemia worldwide. Elevated Hb A₂ is a mark of β-thal carriers. The aim of this study was to identify the pathogenic variants associated with the Hb A₂ levels. One thousand and thirty β-thal carriers were recruited for this study. Using positive natural expression quantitative trait loci (eQTL) analysis, a significant variant was selected. Genotyping for the rs231841 polymorphism was performed by the Sequenom MassARRAY IPLEX platform. All genetic association analyses were performed with the PLINK program. The linear regression analysis showed that rs231841 in the intron region of the potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene on chromosome 11p15 was significantly associated with Hb A₂ levels. The presence of the C allele was associated with elevated Hb A₂ levels. Our results suggest that rs231841 on the KCNQ1 gene with positive natural selection is related to Hb A₂ levels in Chinese β-thal carriers, and KCNQ1 is probably associated with the expression of the β-like globin gene cluster.

Keywords:

• β-Thalassemia (β-thal)
• Hb A₂
• positive natural selection
• rs231841 polymorphism

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

National Natural Science Foundation of China10.13039/501100001809

Guangxi Key Laboratory of Thalassemia Research16-380-34This study was supported by grants from the National Natural Science Foundation of China [No. 81360093] and Guangxi Key Laboratory of Thalassemia Research [16-380-34].