Level of Hemoglobin F and G gamma Gene Expression in Sickle Cell Disease and Their Association with Haplotype and Xmnl Polymorphic Site in South of Iran

Background: Molecular genetic factors regulating hemoglobin F (Hb F) expression are important modifiers of the severity of sickle cell anemia (SS). Methods: The prevalence of XmnI polymorphic site , the Gy:Ay ratio and the Hb F level were determined using PCR-RFLP procedure, HPLC and alkaline denaturation method, respectively, in var ious haplotypes of 52 pat ients with SS, 18 pat ients with sickle/li-thalassemia (S/Thal), 17 with sickle cell trait (AS) and 53 normal subjects from Fars and Khuzestan provinces who attended the Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran during 2002-03. Results: The prevalence of XmnI (+/+) site in patients with SS was 53.8% which was higher than that for S/Thal (23.5 %), AS (22.2%) and normal individuals (7.5%). There was a correlation between the presence of XmnI site and high Gy : ~ ratio in SS and S/Thal patients with Arab-Indian homozygous or heterozygous haplotypes (contingency coefficient=0.43, P=0.002) . In the present study, the Hb F level was sign ificantly higher in SS patients with one or two Arab-Ind ian haplotypes as compared to Bantu , Benin and Cameroon haplotypes. However, the Hb F level was significantly higher in patients with S/Thal having two Xmnl sites carrying Arab-Indian and Senegal haplotypes as compared to Bantu , Benin and Cameroon haplotypes. The increasing effect of presence XmnI s ite on Hb F level appears only when hemolytic stress is present as in SS and S/Thal patients (contingenc gamma coefficient=0.35, P=0.01). Conclusion: Th e presence of XmnI polymorphic s ite in haplotype back grounds of Arab-Indian and Senegal in sickle cell anemia is corre lated with high level of Hb F and G gamma:Ay rat io.