title: Haptoglobin and myeloperoxidase (- G463A) gene polymorphisms in Brazilian sickle cell patients with and without secondary iron overload.
abstract: We aimed to investigate the influence of haptoglobin (Hp) and myeloperoxidase (MPO - G463A; dbSNP rs2333227) gene polymorphisms on 78 sickle cell patients of a public hospital in the Federal District/Brazil with and without iron overload, to evaluate a possible association between these polymorphisms and clinical variability, response to treatment and prognosis. Data were obtained through laboratory tests, questionnaires, research in medical records and analyses of polymorphisms using PCR-based methods. Positive correlations were found between Hp and ferritin levels, hydroxyurea treatment, hospitalisation for and sequelae from stroke; and between MPO and number of hospitalizations in the past 12 months and splenectomy. Significant associations of specific Hp genotypes with comorbidities were also found, while results suggested that MPO AA homozygosis could increase effects of asplenia. Deviation from Hardy-Weinberg equilibrium, compatible with heterozygous deficit, was observed for Hp polymorphism. Odds ratio suggested the possibility that increased chance of hospitalisation for stroke (OR = 6.346; IC 95% = 1.56-25.79; p = 0.005) and sequelae of stroke (OR = 6.556; IC 95% = 1.578-27.237; p = 0.005) could be associated with lower frequency of 1S-2 than expected. In the interaction analyses, significant effects between subjects were shown only in the group without overload for Hp polymorphism in hs-CRP levels (p = 0.000) and number of transfusions (p = 0.018), and for MPO polymorphism (p = 0.000) and the interaction Hp/MPO (p = 0.000) in hs-CRP values. Results corroborate others indicating biological differences between Hp*1 alleles and highlight the importance of this study in understanding the biological significance of Hp and MPO polymorphisms in clinical variability and response to treatment of sickle cell patients.
authors.forename: Lilian Carla
authors.initials: LC
authors.lastname: Barbosa
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: Miranda-Vilela
authors.forename: Cássia de Oliveira
authors.initials: Cde O
authors.lastname: Hiragi
authors.forename: Ieler Ferreira
authors.initials: IF
authors.lastname: Ribeiro
authors.forename: Margarete Barbosa
authors.initials: MB
authors.lastname: Daldegan
authors.forename: Cesar Koppe
authors.initials: CK
authors.lastname: Grisolia
authors.forename: Leopoldo Luiz
authors.initials: LL
authors.lastname: dos Santos-Neto
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000755:Anemia, Sickle Cell / Q000150:complications* / Q000235:genetics* / Q000628:therapy; D001938:Brazil; D003430:Cross-Sectional Studies; D004909:Erythrocyte Indices; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D019190:Iron Overload / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D009195:Peroxidase / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D006242:Haptoglobins; D009195:Peroxidase