University of Khartoum

Association of Hemoglobin F Regulatory Genes Polymorphism and Other Hemoglobinopatheis with Sickle Cell Disease Phenotype in Kassala State

Association of Hemoglobin F Regulatory Genes Polymorphism and Other Hemoglobinopatheis with Sickle Cell Disease Phenotype in Kassala State

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Title: Association of Hemoglobin F Regulatory Genes Polymorphism and Other Hemoglobinopatheis with Sickle Cell Disease Phenotype in Kassala State
Author: Gindil, Badr Eldin Awad Abdelmagid
Abstract: Background Sickle cell disease (SCD) is a genetic disorder involving substitution of glutamic acid by valine at position 6 of β-globin gene resulting in abnormal Hemoglobin S (HbS) which changes the structure of erythrocytes to rigid and sickle cell which induces vaso-occlusive crisis. This mutation may be homozygous (HbSS) or heterozygous, in which other hemoglobin may expressed with S hemoglobin. Hemoglobin Gama2 (HBG2) & B Cell Lymphoma 11A (BCL11A) genes play a role in expression & repression of hemoglobin F respectively. The main objective of this study was to find out the association of hemoglobin F regulatory genes (HBG2&BCL11A ) polymorphism and other hemoglobinopatheis with sickle cell disease phenotype. Materials and Methods This was across-sectional hospital based study, ethical clearance was obtained from ethics committee of the Institute of Endemic Diseases. Blood samples were collected from SCD patients in Kassala and Kuwaiti hospitals in Kassala State (May-October 2014). Complete Hemogram was assessed using Sysmex Cell Counter auto analyzer, Hemoglobin electrophoresis was performed for all samples using cellulose acetate paper method. DNA was extracted using phenol chloroform method. DNA quantity& quality was measured by Nanodrop device. BCL11A and HBG2 genes were amplified using Polymerase Chain Reaction (PCR), PCR products wereanalyzed by gel electrophoresis. HBG2 gene was genotyped by Restriction Fragment Length Polymorphism (RFLP) using Xmn1 enzyme. BCL11a gene was genotyped by sequencing, DNA sequences were analyzed using Bioedit Sequence Alignment editor software. Descriptive & Inferential statistics were done using SPSS V.15. Results Hematological parameters measurement showed the mean ofRBCs count ,Hb and HCT levels in SCA and HbSC were lower than in HbAS and HbSF patients (P<0.001, P=0.002 and P=0.030) respectively. Leukocyte count was significantly higher (P=0.004) in HbSS and HbSC compared to HbAS and HbSF patients. Platelets count was significantly higher in HbSS and HbSF compared to HbAS and HbSC patients (P<0.001).There was no significant association between hemoglobin phenotype and pain episode frequency (P=0.066). Results showed high association between hemoglobin phenotypes and pain severity (P˂0.001, X2=102.121, DF=3), HbSS showed the most severe pain episode followed by HbSC, HbAS and HbSF patiens.Results showed significant association between BCL11A genotypes and frequency of pain (P˂0.001), patients with CC genotype showed higher frequency followed by TC and TT genotypes. There wasa significant association between BCL11A genotypes and pain severity(P<0.001, X2=19.321, DF=2), patients with TT genotype had the most severe pain episode followed by TC and CC genotype. Conclusion SCD patients with BCL11A gene homozygous mutant genotype TT were found to have the most severe pain episode and low pain episode frequency, while the wild homozygous genotype CC had the most pain episode frequency and low pain episode. Anemia and infection showed mostly in HbSS and HbSC patients. Low pain episodes showed in HbSF and HbAS patients.
Description: 79 Pages
URI: http://khartoumspace.uofk.edu/123456789/23837


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