level of hemoglobin f and gg gene expression in sickle cell disease and their association with haplotype and xmni 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 g g: a g ratio and the hb f level were determined using pcr-rflp procedure, hplc and alkaline denaturation method, respectively, in various haplotypes of 52 patients with ss, 18 patients with sickle/β-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 g g: a g 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 significantly higher in ss patients with one or two arab-indian haplotypes as compared to bantu, benin and cameroon haplotypes. however, the hb f level was significantly higher in patients with s/thal having two xmni sites carrying arab-indian and senegal haplotypes as compared to bantu, benin and cameroon haplotypes. the increasing effect of presence xmni site on hb f level appears only when hemolytic stress is present as in ss and s/thal patients (contingency coefficient=0.35, p=0.01).   conclusion: the presence of xmni polymorphic site in haplotype backgrounds of arab-indian and senegal in sickle cell anemia is correlated with high level of hb f and g g: a g ratio.