title: DNA polymorphisms at BCL11A, HBS1L-MYB and Xmn1-HBG2 site loci associated with fetal hemoglobin levels in sickle cell anemia patients from Northern Brazil.
abstract: Increased levels of fetal hemoglobin (HbF, α2γ2) may reduce sickle cell anemia severity due to its ability to inhibit HbS polymerization and also reduce the mean corpuscular HbS concentration. We have investigated the influence of three known major loci on the HbF trait (HBG2, rs748214; BCL11A, rs4671393; and HBS1L-MYB, rs28384513, rs489544 and rs9399137) and HbF levels in SCA patients from the State of Pará, Northern Brazil. Our results showed that high levels of HbF were primarily influenced by alleles of BCL11A (rs4671393) and HMIP (rs4895441) loci, and to a lesser extent by rs748214 Gγ-globin (HBG2) gene promoter. The SNPs rs4671393 and rs4895441 explained 10% and 9.2%, respectively, of the variation in HbF levels, while 4.1% of trait variation was explained by rs748214. The results can be considered as in accordance with the pattern of ancestry displayed by the SCA patients: 39.6% European, 29.6% African and 30.8% Native American, and reinforce the suggestion that studies of association between genetic modifiers and clinical and laboratory manifestations in Brazil must be controlled by ancestry.
authors.affiliation: Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Corrêa, No. 1, Guamá, CEP 66075-110, Belém, PA, Brazil.
authors.forename: Greice Lemos
authors.initials: GL
authors.lastname: Cardoso
authors.affiliation: Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Corrêa, No. 1, Guamá, CEP 66075-110, Belém, PA, Brazil.
authors.forename: Isabela Guerreiro
authors.initials: IG
authors.lastname: Diniz
authors.affiliation: Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Corrêa, No. 1, Guamá, CEP 66075-110, Belém, PA, Brazil.
authors.forename: Aylla Núbia Lima Martins da
authors.initials: AN
authors.lastname: Silva
authors.affiliation: Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Corrêa, No. 1, Guamá, CEP 66075-110, Belém, PA, Brazil.
authors.forename: Daniele Almeida
authors.initials: DA
authors.lastname: Cunha
authors.affiliation: Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Corrêa, No. 1, Guamá, CEP 66075-110, Belém, PA, Brazil.
authors.forename: Josivaldo Soares da
authors.initials: JS
authors.lastname: Silva Junior
authors.affiliation: Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Corrêa, No. 1, Guamá, CEP 66075-110, Belém, PA, Brazil.
authors.forename: Camila Tavares Carvalho
authors.initials: CT
authors.lastname: Uchôa
authors.affiliation: Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Corrêa, No. 1, Guamá, CEP 66075-110, Belém, PA, Brazil.
authors.forename: Sidney Emanuel Batista dos
authors.initials: SE
authors.lastname: Santos
authors.affiliation: Fundação Centro de Hemoterapia e Hematologia do Pará, Travessa Travessa Padre Eutíquio, 2109, Batista Campos, CEP 66033-000, Belém, PA, Brazil.
authors.forename: Saide Maria Sarmento
authors.initials: SM
authors.lastname: Trindade
authors.affiliation: Fundação Centro de Hemoterapia e Hematologia do Pará, Travessa Travessa Padre Eutíquio, 2109, Batista Campos, CEP 66033-000, Belém, PA, Brazil.
authors.forename: Maria do Socorro de Oliveira
authors.initials: Mdo S
authors.lastname: Cardoso
authors.affiliation: Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Rua Augusto Corrêa, No. 1, Guamá, CEP 66075-110, Belém, PA, Brazil.
authors.forename: João Farias
authors.initials: JF
authors.lastname: Guerreiro
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D044383:Black People; D002648:Child; D021901:DNA, Intergenic; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics*; D056426:Genetic Loci; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006801:Humans; D007199:Indians, South American; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D044465:White People; D055545:gamma-Globins / Q000235:genetics*
chemical_list: D021901:DNA, Intergenic; D006451:Hemoglobin, Sickle; D055545:gamma-Globins; D005319:Fetal Hemoglobin
keywords: Brazilian patients; Fetal hemoglobin; Genetic modifier; Sickle cell anemia