title: Contribution of β-globin cluster polymorphisms to raise fetal hemoglobin levels in normal adults.
abstract: Hereditary persistence of fetal hemoglobin (HPFH) is a group of genetically heterogeneous conditions characterized by continued expression of fetal hemoglobin (HbF) in adulthood. HPFH may be due not only to point mutations or large deletions in different regions of the cluster β globin, but also to variations in several polymorphic sequences in this cluster. The objective of this work was to evaluate effects of polymorphic markers within cluster β globin on HbF expression. For the purpose, we have explored in this first study of Tunisian HPFH four polymorphic regions of β globin cluster in 68 healthy adults (34 subjects with high levels of HbF and 34 with normal HbF levels). Our results showed that the increase of HbF levels is associated with the -158 Gγ C → T polymorphism, the TG(18)CG(2)CACG, TC TG(9)AG TG(2)CG(2) and TG(11)CG(4) configurations in the second intron of Gγ gene and the -540 β (AT)(6)T(9) and (AT)(7)T(8) repeated sequences. Among the 34 subjects with raised levels of HbF, approximately 97% carried one or more of these six markers. This study suggests that there is a significant association between certain polymorphic configurations of the β globin cluster and the increase of HbF levels in healthy individuals.
authors.affiliation: Biochemistry Laboratory, Children's Hospital, Bab Saadoun Square, 1007, Tunis, Tunisia. latifa.b.jouini@gmail.com
authors.forename: Latifa
authors.initials: L
authors.lastname: Jouini
authors.forename: Amina
authors.initials: A
authors.lastname: Bibi
authors.forename: Faida
authors.initials: F
authors.lastname: Ouali
authors.forename: Sondess
authors.initials: S
authors.lastname: Hadj Fredj
authors.forename: Fekria
authors.initials: F
authors.lastname: Ouennich
authors.forename: Hajer
authors.initials: H
authors.lastname: Siala
authors.forename: Taieb
authors.initials: T
authors.lastname: Messaoud
authors.forename: Slaheddine
authors.initials: S
authors.lastname: Fattoum
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D005260:Female; D005319:Fetal Hemoglobin / Q000378:metabolism*; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D059372:Nucleotide Motifs / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D055815:Young Adult; D055544:beta-Globins / Q000235:genetics*
chemical_list: D005819:Genetic Markers; D055544:beta-Globins; D005319:Fetal Hemoglobin