A Novel Variant with Positive Natural Selection Influenced Hb A 2 Levels in Chinese Individuals with β-Thalassemia.

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.