Hemoglobin C associated with protection from severe malaria in the Dogon of Mali, a West African population with a low prevalence of hemoglobin S

Abstract

The malaria hypothesis proposes a survival advantage for individuals with hemoglobin variants in areas of endemicPlasmodium falciparum malaria. Hemoglobin C (HbC) is a possible example in West Africa, where this hemoglobin has a centric distribution with high frequencies among certain populations including the Dogon ethnic group. To test whether HbC is associated with protection from malaria, we performed a case-control study in the Dogon of Bandiagara, Mali. HbC was present in 68 of 391 (17.4%) of uncomplicated malaria control cases, whereas it was detected in only 3 of 67 cases (4.5%) of severe malaria (odds ratio [OR], 0.22;P = .01). Further, HbC was present in only 1 of 34 cases (2.9%) with cerebral manifestations, the most common presentation of severe malaria in this population (OR, 0.14; P = .03). Episodes of uncomplicated malaria and parasitemias (4800-205 050/μL) were identified in cases of homozygous HbC (HbCC), which indicates thatP falciparum parasites are able to efficiently replicate within HbCC erythrocytes in vivo. These findings suggest that HbC does not protect against infection or uncomplicated malaria but can protect against severe malaria in the Dogon population of Bandiagara, Mali. The data also suggest that the protective effect associated with HbC may be greater than that of HbS in this population.

Genetic analysis of MDR1 and inflammatory bowel disease reveals protective effect of heterozygous variants for ulcerative colitis

“…39,40 The heterozygous phenotype in sickle cell anemia provides protection against malaria. 41,42 Approximately 1 in 13 African-Americans is a carrier, as their recent ancestry is from malaria-stricken regions. 43 Other We present the hypothesis that heterozygous carriers for certain MDR1 variants are more resistant to bacterial infections than their homozygous counterparts.…”

The role played by natural selection on Mendelian traits in humans

“…32,34 Like HbS, HbC is primarily observed in Africa, although its distribution is virtually restricted to West African groups. 31 Both the heterozygote and homozygote states of HbC have been shown to confer strong protection against severe falciparum malaria, 40,41 with a substantially greater protective effect for homozygotes. 41 In contrast with HbS homozygotes, HbC homozygotes present a much milder phenotype than sickle-cell disease, displaying a relatively mild hemolytic anemia.…”

Erythrocyte variants and the nature of their malaria protective effect

“…This mutation is very common in malarious areas of West Africa, with only mild haematological symptoms in the homozygote (Roberts et al ., 2004). A case-control study performed in the Dogon people of Mali showed a risk reduction of developing severe malaria of 80% for those carrying HbC, when using uncomplicated malaria as the control group (Agarwal et al ., 2000). A second, larger study of the Mossi of Burkina Faso, showed a reduction in clinical malaria of 29% for HbAC individuals and ~ 90% for HbCC (Modiano et al ., 2001).…”