title: 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 β(0)-thalassemia/hemoglobin (Hb) E (β(0)-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.
authors.affiliation: Laboratory of Molecular Biology and Immunology, Department of Pharmacy, School of Health Sciences, University of Patras, University Campus, Rion, Patras, Greece.
authors.forename: Emily
authors.initials: E
authors.lastname: Giannopoulou
authors.forename: Marina
authors.initials: M
authors.lastname: Bartsakoulia
authors.forename: Christina
authors.initials: C
authors.lastname: Tafrali
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kourakli
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Poulas
authors.forename: Eleana F
authors.initials: EF
authors.lastname: Stavrou
authors.forename: Adamantia
authors.initials: A
authors.lastname: Papachatzopoulou
authors.forename: Marianthi
authors.initials: M
authors.lastname: Georgitsi
authors.forename: George P
authors.initials: GP
authors.lastname: Patrinos
mesh_terms: D000483:Alleles; D005787:Gene Frequency; D056726:Genetic Association Studies; D008040:Genetic Linkage; D056426:Genetic Loci; D005838:Genotype; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011544:Pseudogenes; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism
chemical_list: D055544:beta-Globins; D006918:Hydroxyurea