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

Authors

  • A. Vaisi-Raygani
  • M. Haghshenass
  • M. Rezaei
  • Zohreh Rahimi Department of Clinical Biochemistry, Medical School, Daneshgah Avenue, Kermanshah, Iran
Abstract:

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 Gg:Ag 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 Gg:Ag 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 Gg:Ag ratio.

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Journal title

volume 32  issue 4

pages  234- 239

publication date 2007-12-01

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