title: Inheritance of the Bantu/Benin haplotype causes less severe hemolytic and oxidative stress in sickle cell anemia patients treated with hydroxycarbamide.
abstract: Beta S-globin gene cluster haplotypes (β(S)-haplotypes) can modulate the response to hydroxycarbamide (HC) treatment in sickle cell anemia (SCA) patients. In Brazil, the most common haplotypes are Bantu and Benin, and both confer a poor prognosis for patients when untreated with HC. We evaluated oxidative and hemolytic biomarkers in 48 SCA patients undergoing HC treatment separated in three subgroups: Bantu/Bantu, Bantu/Benin and Benin/Benin haplotype. On the basis of reduced haptoglobin (HP) levels, patients with Bantu/Bantu haplotypes had 3.0% higher hemolysis degree when compared with those with Bantu/Benin haplotypes (P=0.01). The Benin/Benin patients had 53.6% greater lipid peroxidation index than the Bantu/Bantu patients (P=0.01) because of evaluated thiobarbituric acid reactive species levels. The Bantu/Benin subgroup had intermediate levels of hemolytic and oxidative stress markers compared with the homozygous subgroups. Through strict inclusion criteria adopted, as well as consolidated and well-described hemolytic and the oxidative parameters evaluated, we suggest a haplotype-interaction response to HC treatment mediated by a 'balance' between the genetic factors of each haplotype studied.
authors.affiliation: Department of Biology, Hemoglobin and Hematological Genetic Diseases Laboratory, Sao Paulo State University (UNESP), Sao Paulo, Brazil.
authors.forename: Jéssika V
authors.initials: JV
authors.lastname: Okumura
authors.affiliation: Department of Biology, Hemoglobin and Hematological Genetic Diseases Laboratory, Sao Paulo State University (UNESP), Sao Paulo, Brazil.
authors.forename: Danilo G H
authors.initials: DG
authors.lastname: Silva
authors.affiliation: Department of Biology, Hemoglobin and Hematological Genetic Diseases Laboratory, Sao Paulo State University (UNESP), Sao Paulo, Brazil.
authors.forename: Lidiane S
authors.initials: LS
authors.lastname: Torres
authors.affiliation: Department of Biology, Hemoglobin and Hematological Genetic Diseases Laboratory, Sao Paulo State University (UNESP), Sao Paulo, Brazil.
authors.forename: Edis
authors.initials: E
authors.lastname: Belini-Junior
authors.affiliation: Department of Biology, Hemoglobin and Hematological Genetic Diseases Laboratory, Sao Paulo State University (UNESP), Sao Paulo, Brazil.
authors.forename: Willian M
authors.initials: WM
authors.lastname: Barberino
authors.affiliation: Department of Biology, Hemoglobin and Hematological Genetic Diseases Laboratory, Sao Paulo State University (UNESP), Sao Paulo, Brazil.
authors.forename: Renan G
authors.initials: RG
authors.lastname: Oliveira
authors.affiliation: Department of Biology, Hemoglobin and Hematological Genetic Diseases Laboratory, Sao Paulo State University (UNESP), Sao Paulo, Brazil.
authors.forename: Gisele C S
authors.initials: GC
authors.lastname: Carrocini
authors.affiliation: Department of Molecular Biology, Sao Jose do Rio Preto Medical School (FAMERP), Sao Paulo, Brazil.
authors.forename: Gabriela B
authors.initials: GB
authors.lastname: Gelaleti
authors.affiliation: Hematological State Institute 'Arthur de Siqueira Cavalcanti' (HEMORIO), Rio de Janeiro, Brazil.
authors.forename: Clarisse L C
authors.initials: CL
authors.lastname: Lobo
authors.affiliation: Department of Biology, Hemoglobin and Hematological Genetic Diseases Laboratory, Sao Paulo State University (UNESP), Sao Paulo, Brazil.
authors.forename: Claudia R
authors.initials: CR
authors.lastname: Bonini-Domingos
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D000986:Antisickling Agents / Q000627:therapeutic use; D015415:Biomarkers; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006239:Haplotypes; D006451:Hemoglobin, Sickle / Q000235:genetics*; D006461:Hemolysis; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D040582:Inheritance Patterns; D015227:Lipid Peroxidation; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D018384:Oxidative Stress; D010641:Phenotype; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000986:Antisickling Agents; D015415:Biomarkers; D006451:Hemoglobin, Sickle; D006918:Hydroxyurea