title: Chronic inflammatory state in sickle cell anemia patients is associated with HBB(*)S haplotype.
abstract: The chronic inflammatory state in sickle cell anemia (SCA) is associated with several factors such as the following: endothelial damage; increased production of reactive oxygen species; hemolysis; increased expression of adhesion molecules by leukocytes, erythrocytes, and platelets; and increased production of proinflammatory cytokines. Genetic characteristics affecting the clinical severity of SCA include variations in the hemoglobin F (HbF) level, coexistence of alpha-thalassemia, and the haplotype associated with the HbS gene. The different haplotypes of SCA are Bantu, Benin, Senegal, Cameroon, and Arab-Indian. These haplotypes are associated with ethnic groups and also based on the geographical origin. Studies have shown that the Bantu haplotype is associated with higher incidence of clinical complications than the other haplotypes and is therefore considered to have the worst prognosis. This study aimed to evaluate the profile of the proinflammatory cytokines interleukin-6, tumor necrosis factor-α, and interleukin-17 in patients with SCA and also to assess the haplotypes associated with beta globin cluster S (HBB(*)S). We analyzed a total of 62 patients who had SCA and had been treated with hydroxyurea; they had received a dose ranging between 15 and 25 (20.0±0.6)mg/kg/day for 6-60 (18±3.4)months; their data were compared with those for 30 normal individuals. The presence of HbS was detected and the haplotypes of the beta S gene cluster were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Our study demonstrated that SCA patients have increased inflammatory profile when compared to the healthy individuals. Further, analysis of the association between the haplotypes and inflammatory profile showed that the levels of IL-6 and TNF-α were greater in subjects with the Bantu/Bantu haplotype than in subjects with the Benin/Benin haplotype. The Bantu/Benin haplotype individuals had lower levels of cytokines than those with the Bantu/Bantu haplotype and greater levels than those of subjects with the Benin/Benin haplotype. For IL-17, a slight trend toward decreased levels was observed in the subjects with the Benin/Benin haplotype, when compared to those with the Bantu/Bantu and Bantu/Benin haplotypes; however, this difference was not statistically significant. Our results show that genetic polymorphisms in sickle cell anemia are associated with the inflammatory profile.
authors.affiliation: Post-Graduate Program in Pathology, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address: izabelcristina.farmacia@yahoo.com.br.
authors.forename: Izabel C J
authors.initials: IC
authors.lastname: Bandeira
authors.affiliation: Post-Graduate Program in Development and Technological Innovation in Drugs, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Lillianne B S
authors.initials: LB
authors.lastname: Rocha
authors.affiliation: Post-Graduate Program in Pharmaceutical Sciences, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Maritza C
authors.initials: MC
authors.lastname: Barbosa
authors.affiliation: Post-Graduate Program in Development and Technological Innovation in Drugs, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Darcielle B D
authors.initials: DB
authors.lastname: Elias
authors.affiliation: Post-Graduate Program in Pathology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: José A N
authors.initials: JA
authors.lastname: Querioz
authors.affiliation: Post-Graduate Program in Pathology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Max Vitor Carioca
authors.initials: MV
authors.lastname: Freitas
authors.affiliation: Post-Graduate Program in Pathology, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Romélia P
authors.initials: RP
authors.lastname: Gonçalves
mesh_terms: D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D002877:Chromosomes, Human / Q000235:genetics; D002908:Chronic Disease; D016207:Cytokines / Q000097:blood; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D055815:Young Adult; D055544:beta-Globins / Q000235:genetics*
chemical_list: D016207:Cytokines; D055544:beta-Globins; D006918:Hydroxyurea
keywords: Cytokines; HBB(*)S gene haplotype; Inflammation; Sickle cell anemia