The Senegal DNA haplotype is associated with the amelioration of anemia in African-American sickle cell anemia patients

Abstract

We have previously determined that in African sickle cell anemia (SS) patients three different beta-like globin gene cluster haplotypes are associated with different percent G gamma (one of the two types of non- alpha chains comprising hemoglobin F [HbF]), mean percent HbF, and percent dense cells. We report now that in adult New York SS patients, the presence of at least one chromosome with the Senegal haplotype is associated with higher Hb levels (1.2 g/dL higher) than is found for any other non-Senegal haplotype (P less than .004). The percent reticulocytes and the serum bilirubin levels were lower in these patients. When the effect of alpha-gene number was analyzed by examining a sample of SS patients with concomitant alpha-thalassemia, the same results were obtained. Because the HbF level is significantly higher among the Senegal haplotype carriers in this sample, the inhibitory effect on sickling of this Hb variant may be one of the reasons for the haplotype effect. We conclude that the Senegal beta- like globin gene cluster haplotype is associated with an amelioration of the hemolytic anemia that characterizes sickle cell disease.

Definition and Clinical Importance of Haplotypes

“…However, there are instances in which haplotypes rather than genotypes at a single locus can predict severity of disease. For example, some research suggests that a specific β-globin locus haplotype is associated with less severe sickle cell disease phenotypes (69,70). More recently, a promoter region haplotype in IL10 was associated with a lower incidence of graft-versushost disease and death compared with other haplotypes among patients receiving hematopoietic-cell transplants (43).…”

The Normal Structure and Regulation of Human Globin Gene Clusters

“…The types of genes that surround the α-like and β-like globin gene clusters are quite different (Figure 3.3). The β-like globin gene cluster is surrounded by olfactory receptor (OR) genes, which encode G-protein coupled receptors expressed in olfactory epithelium (39). Several OR gene clusters containing about a thousand genes and pseudogenes are found in the human genome.…”

“…ancestry exhibit wide variations in HbF levels (37)(38)(39)(40). In the United States, pediatric levels vary from 3 to 20% of total hemoglobin, compared with only 0.5-2% for nonanemic individuals.…”

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).…”