The hematologic characteristics of sickle cell anemia bearing the Bantu haplotype: the relationship between G gamma and HbF level

Abstract

Previous work has demonstrated that the HbS gene has appeared and expanded three times in Africa in three separate geographic locations and that these three distinct mutational events can be identified by linked DNA polymorphic sites (haplotypes) surrounding the abnormal gene. We have reported that the Senegalese and Beninian haplotypes differ in G gamma expression, mean percentage of HbF, and percentage of dense cells. We now report on the third haplotype, the Bantu, and find that it has intermediate features, namely, the high mean percentage of HbF and low percentage of dense cells associated with the Senegalese haplotype, but with a low percentage of G gamma expression similar to the Beninian haplotype. The distribution of percent HbF is quite different from Senegal haplotype-bearing sickle cell anemia patients since it covers a much wider range. The low G gamma expression is also different from the Beninians since it contains a significant and unique cluster of individuals with lower than 38% G gamma. Interestingly, among the Bantu there is a strong correlation between HbF levels and G gamma expression, which is not seen with the other haplotypes. These findings open the possibility that among the Bantu haplotype-bearing individuals two chromosomal types exist that define different levels of G gamma and HbF expression. Further structural exploration of these two potential subhaplotypes is needed.

Biological impact of α genes, β haplotypes, and G6PD activity in sickle cell anemia at baseline and with hydroxyurea

“…13 These distinct mutational events were identified by linked DNA polymorphic sites, located on the b-globin cluster, and defined as the Senegal (SEN), Benin (BEN), Bantu/Central African Republic (CAR), and Cameroon 14 haplotypes. Only a few older studies investigated the role of b haplotypes, [15][16][17] but the positive association between HbF level and the number of SEN haplotypes was clearly demonstrated. 15,16 In the United States, the BEN haplotype is largely predominant, the CAR haplotype is rarely observed, and patients are often compound heterozygotes.…”

Sickle cell disease in Uganda: a time for action

“…Molecular variation:The HbS mutation has arisen independently in several geographical locations. Structural variations in the DNA molecule flanking the beta globin gene, referred to as the beta globin haplotypes, are named after the areas where they were first described i.e Senegal, Benin and Bantu (13)(14)(15)(16)(17). The Senegal haplotype occurs on the Atlantic coast of West Africa the Benin haplotype in Central West Africa especially Ghana, Nigeria, and Cotê D'lvoire and the Bantu or Central African Republic haplotype in the Democratic Republic of Congo, the Central African Republic, Angola and Kenya (18).…”

Sickle cell disease in the older adult

“…1), and 67 years for adults with HbSS/HbSb 0 for a single centre in the UK. 6 Nevertheless, the life expectancy of an individual with SCD lags behind that of the general population by [20][21][22][23][24][25][26][27][28][29][30] years. 7 By their fifth decade, half of the surviving patients will have suffered documented irreversible damage to one or more organs due to ongoing vasculopathy.…”

“…26 Patients with SEN or AI types have the highest HbF levels and milder disease, while those with CAR haplotypes have lower HbF levels with generally more severe disease. 27,28 HbF levels impact the 'primary' level of disease pathology, HbS polymerisation, thus HbF levels have a global beneficial effect. Indeed, in SCD, high HbF levels are a major predictor of survival, 4,6 and reduced pain; 29 conversely, low levels of HbF have been associated with increased risk of brain infarcts in young children.…”