title: Sequence change in the HS2-LCR and Ggamma-globin gene promoter region of sickle cell anemia patients.
abstract: The fetal hemoglobin (HbF) levels and betaS-globin gene haplotypes of 125 sickle cell anemia patients from Brazil were investigated. We sequenced the Ggamma- and Agamma-globin gene promoters and the DNase I-2 hypersensitive sites in the locus control regions (HS2-LCR) of patients with HbF level disparities as compared to their betaS haplotypes. Sixty-four (51.2%) patients had CAR/Ben genotype; 36 (28.8%) Ben/Ben; 18 (14.4%) CAR/CAR; 2 (1.6%) CAR/Atypical; 2 (1.6%) Ben/Cam; 1 (0.8%) CAR/Cam; 1 (0.8%) CAR/Arab-Indian, and 1 (0.8%) Sen/Atypical. The HS2-LCR sequence analyses demonstrated a c.-10.677G>A change in patients with the Ben haplotype and high HbF levels. The Gg gene promoter sequence analyses showed a c.-157T>C substitution shared by all patients, and a c.-222_-225del related to the Cam haplotype. These results identify new polymorphisms in the HS2-LCR and Gg-globin gene promoter. Further studies are required to determine the correlation between HbF synthesis and the clinical profile of sickle cell anemia patients.
authors.affiliation: Laboratório de Patologia e Biologia Molecular, Centro de Pesquisas Gonçalo Moniz, FIOCRUZ, Salvador, BA, Brasil.
authors.forename: E V
authors.initials: EV
authors.lastname: Adorno
authors.forename: J P
authors.initials: JP
authors.lastname: Moura-Neto
authors.forename: I
authors.initials: I
authors.lastname: Lyra
authors.forename: A
authors.initials: A
authors.lastname: Zanette
authors.forename: L F O
authors.initials: LF
authors.lastname: Santos
authors.forename: M O
authors.initials: MO
authors.lastname: Seixas
authors.forename: M G
authors.initials: MG
authors.lastname: Reis
authors.forename: M S
authors.initials: MS
authors.lastname: Goncalves
mesh_terms: D000328:Adult; D000755:Anemia, Sickle Cell / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003850:Deoxyribonuclease I / Q000235:genetics*; D005319:Fetal Hemoglobin / Q000032:analysis; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D019901:Locus Control Region / Q000235:genetics*; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D005819:Genetic Markers; D005914:Globins; D005319:Fetal Hemoglobin; D003850:Deoxyribonuclease I