β-Globin Gene Cluster Haplotypes in a Cohort of 221 Children with Sickle Cell Anemia or Sβ⁰-Thalassemia and Their Association with Clinical and Hematological Features

Abstract

Background/Aims: β^S-Haplotype prevalence and its associations with clinical and hematological characteristics were assessed in Brazilian children with sickle cell anemia or Sβ⁰-thalassemia. Methods: A retrospective randomized cohort study was undertaken with 208 SS and 13 Sβ⁰-thalassemia children derived from the Newborn Screening Program of the state of Minas Gerais. β^S-Haplotypes were determined by PCR-RFLP. Results: Thirty-nine percent of the SS subjects had the CAR/CAR genotype, 33% had CAR/Ben, 24% had Ben/Ben, 1% had CAR/Atp, 1% had Ben/Atp, and 1% had Arab-Indian/Ben; 1% could not be characterized. Of the Sβ⁰-thalassemia children, 5 were CAR/undefined, 2 were Ben/undefined, and 1 was CAM/undefined. There was no significant association between β^S-haplotypes and the total Hb, Hb F, MCV, MCH, WBC, and reticulocyte count among the SS children. Likewise, no significant association was detected between β^S-haplotypes and the frequency of acute chest syndrome episodes, blood transfusions, splenic sequestration, or cerebrovascular disease (high-risk/conditional transcranial Doppler ultrasonography or clinical stroke). A limited number of Sβ⁰-thalassemia children precluded valid analyses. Conclusions: The prevalence of β^S-haplotypes in this study is in agreement with the historical records of African slaves brought to the state of Minas Gerais. Furthermore, β^S-haplotypes CAR and Ben were not associated with any analyzed feature of children with sickle cell anemia.

Coinheritance of α-Thalassemia Decreases the Risk of Cerebrovascular Disease in a Cohort of Children with Sickle Cell Anemia

“…Therefore, the study population consisted of 221 children, 208 carrying Hb SS and 13 with Hb S-β 0 -thal. The prevalence of the Bantu or Central African Republic (CAR), Benin, Arabian Indian and atypical haplotype alleles in the 208 Hb SS children was 0.57, 0.42, 0.005, and 0.01, respectively (28).…”

“…The selection methodology of study populations has been described previously (28). Briefly, from about 1.2 million children born between January 1 1999 and December 31 2006, 864 were diagnosed with sickle cell disease at the NSP-MG and scheduled for their first clinical appointment in the outpatient care unit of the HEMOMINAS Foundation (Hemoceter of Minas Gerais) in Belo Horizonte, state of Minas Gerais, Brazil.…”

“…The β S allele genotype of all subjects was confirmed by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) as previously described (28,29). For α-thal genotyping, fragments of DNA resulting from the seven more frequent deletions [-α 3.7 , -α 4.2 , --SEA , --FIL , --MED , -(α) 20.5 and --THAI ] were amplified using the m-PCR (QIAGEN ® Multiplex PCR kit; Qiagen) protocol previously described (30), increasing the primers' annealing temperature to 62 • C.…”

Alpha-thalassemia protects against cerebrovascular disease in children with sickle cell anemia

“…In our study, the data regarding β S -haplotypes were analyzed in several ways, and none showed a significant association between haplotypes and CVD 3 . The only current evidence on the association between β S -haplotypes and SCA phenotype is their relationship to the level of Hb F. However, the Hb F concentration seems to have no association with CVD 5 .…”

“…Recently, Filho et al found that Bantu/Atypical β S -globin gene cluster haplotype (β S -haplotype) was associated with the occurrence of CVD, and alpha-thalassemia (α-thal) was not 2 . We also have studied the influence of β S -haplotype and α-thal on CVD in a cohort of 208 children with SCA from Minas Gerais state, Brazil, and published it in 2010 3,4 . In our experience, α-thal genotypes were significantly associated with reduction in CVD risk 4 .…”