Increased γ‐globin gene expression in β‐thalassemia intermedia patients correlates with a mutation in 3′HS1

We report a novel set of genetic markers in the DNaseI hypersensitive sites comprising the human β‐globin locus chromatin hub (CH), namely HS‐111 and 3′HS1. The HS‐111 (−21 G>A) and 3′HS1 (+179 C>T) transitions form CH haplotypes, which occur at different frequencies in β‐thalassemia intermedia and major patients and normal (nonthalassemic) individuals. We also show that the 3′HS1 (+179 C>T) variation results in a GATA‐1 binding site and correlates with increased fetal hemoglobin production in β‐thalassemia intermedia patients. In contrast, the HS‐111 (+126 G>A) transition, found in three normal chromosomes, is simply a rare polymorphism. We conclude that the CH haplotypes are useful genetic determinants for β‐thalassemia major and intermedia patients, while the 3′HS1 (+179 C>T) mutation may have functional consequences in γ‐globin genes expression. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.