Clinical and molecular characteristics of sickle cell anemia in the northeast of Brazil

Abstract

Beta S-globin gene (β S -globin) haplotypes, markers for severe sickle cell anemia (SCA), and the alpha-thalassemia 2 gene 3.7 kb deletion (-α 2 3.7 kb thal) along with demographic and clinical data were investigated in SCA outpatients (n = 125, 63 female and 62 male) in the Brazilian state of Bahia, which has a high prevalence SCA. PCR-RFLP showed that the Central African Republic/Benin (CAR/BEN, 51.2%) haplotype was most frequent, followed by the Benin/Benin (Ben/Ben, 28.8%). At least one CAR haplotype was present in every outpatient with a history of cerebrovascular accident. The Cameroon (Cam), Senegal (Sen) and Arab-India haplotypes occurred in small numbers, as did atypical haplotypes. Fetal hemoglobin (HbF, %) was unevenly distributed. Compared to those > 18 y, those aged ≤ 18 y had had fewer erythrocyte transfusions and high HbF levels (12.3% ± 7.01 to 7.9% ± 4.36) but a higher frequency of spleen sequestration and pneumonia. Compared with normal α -genes carriers values, the outpatients with -α 2 3.7 kb thal (determined by PCR analysis) had significantly higher mean hemoglobin concentration (Hb) (8.3 ± 1.34 g/dL, p = 0.018) and packed cell volume (PCV = 27.1% ± 4.26, p = 0.019) but low mean corpuscular volume (MCV = 86.1 fL = 10 -15 L ± 9.56, p = 0.0004) and mean corpuscular hemoglobin (MCH = 26.6% ± 4.60, p = 0.039).

The frequency of β-globin gene haplotypes, α-thalassemia and genetic polymorphisms of methylenetetrahydrofolate reductase, factor V Leiden and prothrombin genes in children with sickle cell disease in Rio de Janeiro, Brazil

“…The Cameroon and Arab/Indian haplotypes have also been sporadically reported in Brazil. 4 Although Rio de Janeiro is the second largest Brazilian city and its inhabitants reflect the enormous miscegenation that occurred in Brazil, our results are in agreement with historical reports of the slave trade expressed by a high proportion of the CAR/Bantu haplotype, followed by the Benin haplotype.…”

“…The β-globin haplotype distribution represents a profile of the geographical origin of Africans who were brought to Brazil with a high proportion of CAR/Bantu haplotypes being found in all Brazilian regions. The Benin haplotype is mainly found in the northeast, 4 while the Senegal haplotype is more common in the north. The Cameroon and Arab/Indian haplotypes have also been sporadically reported in Brazil.…”

Beta-Globin Gene Haplotypes Among Cameroonians and Review of the Global Distribution: Is There a Case for a Single Sickle Mutation Origin in Africa?

“…Further genetic studies in well-defined populations from across Africa are urgently needed, to allow determination of the exact extent of the spread of various HBB haplotypes, as this would help to identify the mutation's geographical origin precisely, and to explore the recent increase in frequency of the b(S) mutation, irrespective of its haplotypic background. The data reported here emphasize the need to re-explore the origin of sickle cell mutation as well as past and recent evolutionary dynamics of African human populations, as this could yield important information about the evolutionary history of SCD, which of course hold significant clinical relevance (Adorno et al, 2008).…”

“…The Cameroon haplotype has previously been associated with poor clinical outcome and increased stoke episodes in SCD (Adorno et al, 2008;Steinberg et al, 1998), whereas the Benin haplotype is thought to confer a relatively favorable clinical outcome (Steinberg, 2009). In a previous report, we anticipated that the relatively high prevalence of stroke in SCD patients in Cameroon could be attributed to the high proportion of Cameroonian haplotype (Njamnshi et al, 2006).…”

Reply: Genetic polymorphisms and cerebrovascular disease in children with sickle cell anemia from Rio de Janeiro, Brazil

“…Bernaudin et al report that in France, β S haplotypes were not related to CVD 9 . In Brazil (Salvador), at least one chromosome Bantu was observed in patients with a history of CVD 11 . In the United States, a higher risk for CVD development was observed in children with four or more alpha genes whose haplotypes were Bantu/Benin, Atypical or Bantu/Bantu than in children with other associations 6 .…”