title: The XmnI (G)gamma polymorphism influences hemoglobin F synthesis contrary to BCL11A and HBS1L-MYB SNPs in a cohort of 57 beta-thalassemia intermedia patients.
abstract: The HbF level is a quantitative trait influenced by many loci inside or outside the beta-globin gene cluster. The aim of this study was to analyze in 57 beta-thalassemia intermedia patients with very various genotypes the effects on fetal hemoglobin levels of SNPs lying in three genes or chromosome regions which include the XmnI (G)gamma polymorphism at position -158 of the HBG2 promoter (rs7482144), two SNPs located in the BCL11A region (rs4671393 and rs11886868) and three SNPs located in the HBS1L-MYB region (rs28384513, rs9399137 and rs4895441). Our study shows a strong correlation between the XmnI (G)gamma polymorphism and the fetal hemoglobin expression in this patient population (p=0.002). Unfortunately, although recent studies clearly showed a role of SNPs in BCL11A and a HBS1L-MYB region on either clinical expression or fetal hemoglobin levels of beta-hemoglobinopathies such as sickle cell disease and beta-thalassemia, SNPs in BCL11A and the HBS1L-MYB region did not show statistically significant correlations with fetal hemoglobin levels. This suggests that the BCL11A and HBS1L-MYB loci have a minor effect on HbF level compared to the XmnI QTL in beta-thalassemia intermedia patients.
authors.affiliation: Hôpital Edouard Herriot, Hospices Civils de Lyon and Université Claude Bernard, France.
authors.forename: Thi Khanh Tien
authors.initials: TK
authors.lastname: Nguyen
authors.forename: Philippe
authors.initials: P
authors.lastname: Joly
authors.forename: Claire
authors.initials: C
authors.lastname: Bardel
authors.forename: Mustapha
authors.initials: M
authors.lastname: Moulsma
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bonello-Palot
authors.forename: Alain
authors.initials: A
authors.lastname: Francina
mesh_terms: D000755:Anemia, Sickle Cell; D002352:Carrier Proteins; D015331:Cohort Studies; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics*; D005602:France; D005838:Genotype; D006801:Humans; D008297:Male; D009687:Nuclear Proteins; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012097:Repressor Proteins; D013789:Thalassemia / Q000235:genetics*; D055542:alpha-Globins / Q000235:genetics; D055544:beta-Globins / Q000235:genetics
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D055542:alpha-Globins; D055544:beta-Globins; D005319:Fetal Hemoglobin