Comparison of the relative quantities of gamma-mRNAs and fetal hemoglobin in SS patients with different haplotypes.

We have studied the relative levels of gamma-mRNA [%gamma/(gamma + beta)], Ggamma- and Agamma-mRNAs [%Ggamma/(Ggamma + Agamma)], hemoglobin (Hb) F, and the Ggamma and Agamma chains in some 50 patients with sickle cell anemia (SS) and with different haplotypes. As expected, the Hb F levels varied greatly and were high in patients with the Saudi Arabian-Indian haplotype. Similarly, the Ggamma values varied greatly (from 19.5 to 76.5%) and depended on the haplotypes. A rare haplotype, named Mor, was found in 3 SS patients, 1 of whom was a homozygote Mor/Mor; this haplotype is associated with the lowest Ggamma value (19.5% in the homozygote) and with a C-->T mutation at position -202 of the Agamma promoter. The levels of gamma-mRNA roughly parallel those of Hb F, but older patients have increased levels of mRNA, which appears not to be efficiently translated into Hb F. Similar observation have been reported for other hemoglobinopathies such as deltabeta-thalassemia heterozygotes and Hb Lepore heterozygotes. The relative quantity of Ggamma-mRNA was closely related to that of the Ggamma chain in the 15 patients who were studied; the Ggamma- to Agamma-mRNA ratio did not change with age.