title: Variability of hemoglobin F expression in hemoglobin EE disease: hematological and molecular analysis.
abstract: Although the molecular basis of variability of hemoglobin (Hb) F has been extensively examined in β-thalassemia and sickle cell diseases, less study has been done on Hb E disorder. To address the variability of Hb F expression in Hb EE disease, we have examined multiple single nucleotide polymorphisms (SNPs) in the β-globin gene cluster, BCL11A and HBS1L-MYB genes and determined their associations with Hb F levels in this syndrome. Study was done on 141 adult Thai individuals with homozygous Hb E. Hematological parameters were recorded and Hb F measured using Hb-HPLC analyzer. It was found in 26 cases that co-inheritance of α-thalassemia could lead to significant lower production of Hb F. Association of Hb F expression with the (G)γ-Xmn I polymorphism and other SNPs including rs2297339, rs2838513, rs4895441 and rs9399137 in HBS1L-MYB gene and rs4671393 and rs11886868 in BCL11A gene was therefore analyzed in the remaining 115 cases without α-thalassemia. It was found that 4 of these 7 SNPs including (G)γ-XmnI polymorphism (rs7482144), HBS1L-MYB (rs4895441) and (rs9399137) and BCL11A (rs4671393) were significantly associated with higher proportions of subjects with high Hb F (Hb F≥5%). The result demonstrated that multiple genetic modifying factors including T allele of (G)γ-XmnI polymorphism (rs7482144), G allele of HBS1L-MYB (rs489441), C allele of HBS1L-MYB (rs9399137) and C allele of BCL11A (rs4671393) are associated with increased Hb F and in combination could explain approximately 80% of the variation of Hb F in Hb EE disease in Thai population. Other genetic factors regulating Hb F expression in this common genetic disorder remains to be elucidated.
authors.affiliation: Biomedical Sciences Program, Graduate School, Khon Kaen University, Thailand; Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Naruwat
authors.initials: N
authors.lastname: Pakdee
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Supawadee
authors.initials: S
authors.lastname: Yamsri
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Goonnapa
authors.initials: G
authors.lastname: Fucharoen
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Kanokwan
authors.initials: K
authors.lastname: Sanchaisuriya
authors.affiliation: Laboratoire de Génétique, APHP, Groupe Hospitalier Henri Mondor and Université Paris Est Créteil (UPEC), France.
authors.forename: Serge
authors.initials: S
authors.lastname: Pissard
authors.affiliation: Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand. Electronic address: supan@kku.ac.th.
authors.forename: Supan
authors.initials: S
authors.lastname: Fucharoen
mesh_terms: D000483:Alleles; D004909:Erythrocyte Indices; D005319:Fetal Hemoglobin / Q000235:genetics*; D005786:Gene Expression Regulation; D005787:Gene Frequency; D005838:Genotype; D006446:Hemoglobin E / Q000235:genetics*; D006453:Hemoglobinopathies / Q000097:blood / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D055542:alpha-Globins / Q000235:genetics; D017085:alpha-Thalassemia / Q000097:blood / Q000235:genetics; D055544:beta-Globins / Q000235:genetics
chemical_list: D055542:alpha-Globins; D055544:beta-Globins; D006446:Hemoglobin E; D005319:Fetal Hemoglobin
keywords: (G)γ-XmnI polymorphism; BCL11A polymorphism; Genetic modifying factors; HBS1L-MYB polymorphism; Hb F; Homozygous Hb E