title: Molecular characterization of sickle cell anemia in the Northern Brazilian state of Pará.
abstract: To assess alpha+-thalassemia deletion alleles, beta-thalassemia mutations and haplotypes linked to the HBB*S cluster in a sample of 130 unrelated sickle cell anemia (SCA) patients (55% female) from Belém, Pará State, for their possible effects on the patients' survival. -alpha(3.7), -alpha(42), -alpha(20.5), and -(MED) alpha+-thalassemia deletion alleles were investigated using multiplex gap-PCR method. Characterization of beta-thalassemia mutations was made by direct genomic sequencing of the beta-globin gene amplified through polymerase chain reaction (PCR). Haplotypes were determined by analysis of six polymorphic restriction sites [(1) XmnI-5'gammaG, (2) HindIII-gammaG, (3) HindIII-gammaA, (4) HincII-psibeta, (5) HincII-3'psibeta, and (6) HinfI-5'beta] followed by restriction digestion and agarose gel electrophoresis. Twenty-one patients (16%) presented -alpha3.7 thalassemia. Sixteen of those (76%) were heterozygous (-alpha3.7/alphaalpha) and 5 (24%) were homozygous (-alpha3.7/-alpha3.7). -Alpha(4.2), -alpha(20.5) and -(MED) deletions were not found. Nine cases of sickle cell-beta thalassemia were found and four different beta-thal mutations were identified: beta(+) -88 (C>T), 3.8%; beta(+) codon 24 (T > A), 1.5%; beta(+) IVSI-110 (G > A), 0.7% and beta (IVSI-1 (G > A), 0.7%. No differences according to age were observed in -alpha(3.7) deletion, beta-thalassemia and HHB*S haplotypes distribution. Our results suggest that although alpha- and beta-thalassemia and betaS haplotypes may have modulating effect on clinical expression and hematological parameters of SCA, these genetic variables probably have little influence on the subjects' survival.
authors.affiliation: Laboratory of Human and Medical Genetics, Institute for Biological Sciences, Federal University of Pará, Belém, Pará, Brazil.
authors.forename: Greice
authors.initials: G
authors.lastname: De Lemos Cardoso
authors.forename: João Farias
authors.initials: JF
authors.lastname: Guerreiro
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000755:Anemia, Sickle Cell / Q000208:ethnology / Q000235:genetics* / Q000401:mortality; D001938:Brazil / Q000208:ethnology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D055815:Young Adult; D017085:alpha-Thalassemia / Q000208:ethnology / Q000235:genetics*; D017086:beta-Thalassemia / Q000208:ethnology / Q000235:genetics*