Strong linkage disequilibrium of a HbE variant with the (AT) <inf>9</inf>(T)<inf>5</inf> repeat in the BP1 binding site upstream of the β-globin gene in the Thai population

Abstract

A binding site for the repressor protein BP1, which contains a tandem (AT)x(T)y repeat, is located approximately 530 bp 5′ to the human β-globin gene (HBB). There is accumulating evidence that BP1 binds to the (AT)9(T)5 allele more strongly than to other alleles, thereby reducing the expression of HBB. In this study, we investigated polymorphisms in the (AT)x(T)y repeat in 57 individuals living in Thailand, including three homozygotes for the hemoglobin E variant (HbE; β26Glu- > Lys), 22 heterozygotes, and 32 normal homozygotes. We found that (AT)9(T)5 and (AT) 7(T)7 alleles were predominant in the studied population and that the HbE variant is in strong linkage disequilibrium with the (AT) 9(T)5 allele, which can explain why the βE chain is inefficiently synthesized compared to the normal βA chain. Moreover, the mildness of the HbE disease compared to other hemoglobinopathies in Thai may be due, in part, to the presence of the (AT) 9(T)5 repeat on the HbE chromosome. In addition, a novel (AC)n polymorphism adjacent to the (AT)x(T)y repeat (i.e., (AC)3(AT)7(T)5) was found through the variation screening in this study. © The Japan Society of Human Genetics and Springer-Verlag 2004.