A Single Nucleotide Polymorphism in the HBBP1 Gene in the Human β-Globin Locus is Associated with a Mild β-Thalassemia Disease Phenotype

Abstract

The rs2071348 (g.5264146A>C) polymorphism on the HBB pseudogene, namely HBBP1, previously emerged as a variant significantly associated with a milder disease phenotype in Asian β⁰-thalassemia/hemoglobin (Hb) E (β⁰-thal/Hb E [β26(B8)Glu→Lys, GAG>AAG]) patients. In this study, we aimed to explore the possible association of rs2071348 with β-thalassemia (β-thal) disease severity in a group of β-thal major (β-TM) patients (severe phenotype) and β-thal intermedia (β-TI) patients (mild phenotype) of Hellenic origin and compare the results with normal (non thalassemic) individuals of the same origin. In addition, we explored whether this single nucleotide polymorphism (SNP) can be exploited as a pharmacogenomic marker to predict the outcome of Hb F-augmenting therapy in β-thal patients receiving hydroxyurea (HU). Our data suggest that the rs2071348 polymorphism is associated with higher Hb F levels and a milder β-thal disease phenotype. However, the rs2071348 polymorphism in the HBBP1 gene does not correlate with response to HU treatment.

• β-Thalassemia (β-thal)
• HBBP1 Gene
• Polymorphism
• Pharmacogenomics
• Hydroxyurea (HU)
• β-Thalassemia major (β-TM)
• β-Thalassemia intermedia (β-TI)

ACKNOWLEDGMENTS

We cordially thank Professor Emeritus Aglaia Athanassiadou and Dr. Lamprini Psiouri (University of Patras, School of Medicine, Patras, Greece) for their expertise and assistance with samples from hemoglobinopathies patients.

Declaration of Interest: Part of this study was supported by a Research Promotion Foundation (ΠΔE046_02) and European Commission (FP7-200754) grants to GPP. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.