Analysis of hemoglobin F production in Saudi Arabian families with sickle
cell anemia
BA Miller, M Salameh, M Ahmed, N Olivieri, G Antognetti, SH Orkin, TH Huisman and DG Nathan
Erythrocytes and progenitor-derived erythroblasts of sickle cell anemia
patients from the Eastern Province of Saudi Arabia contain increased fetal
hemoglobin and G gamma globin. A distinctive DNA polymorphism haplotype in
the beta globin gene cluster (++- +-), tightly coupled to a C----T
substitution at position -158 5' to the cap site of the G gamma globin
gene, is strongly associated with sickle cell disease in this region. To
determine whether the increased fetal hemoglobin production and/or elevated
G gamma globin content are tightly linked to this haplotype, we studied 55
members of five Saudi families in which sickle cell disease is present. The
results did not suggest a tight linkage of the haplotype to increased fetal
hemoglobin production. On the other hand, several sickle trait family
members heterozygous for the haplotype had normal fetal hemoglobin
production in culture but elevated G gamma to A gamma ratios in peripheral
blood. This observation suggests that in this genetic background increased
expression of the G gamma globin gene may occur without a measurable
increase in total fetal hemoglobin production. The family studies also
clearly demonstrate that increased fetal hemoglobin production by erythroid
progenitors is dependent on zygosity for the sickle gene in this
population. These findings strongly suggest that other factors, such as the
products of genes stimulated by hemolytic stress or other genetic
determinants associated with the Saudi beta S chromosome, may interact with
the -158 C----T substitution and influence gamma globin gene expression in
this population.
Volume 70,
Issue 3,
pp. 716-720,
09/01/1987
Copyright © 1987 by The American Society of Hematology
