School of Biomedical and Allied Health Sciences

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    Association of Endothelial Nitric Oxide Synthase (Enos) Gene Polymorphism with Complications of Hbss in Ghanaian Sickle Cell Disease Patients
    (University of Ghana, 2014-07) Antwi-Boasiako, C.; Antwi, D. A.; Dzudzor, B.; Ekem, I.; University of Ghana, College of Health Sciences , School of Biomedical and Allied Health Sciences , Department of Physiology
    Nitric oxide (NO) is a potent vasodilator synthesized by endothelial nitric oxide synthase (eNOS) enzyme of the vascular endothelial cells and plays a significant role in the regulation of vascular homeostasis by attenuating leukocyte adhesion to the endothelium. Nitric oxide levels are found to be low in Sickle cell disease (SCD) patients. The eNOS gene polymorphism has been implicated. Moreover, very scanty data with conflicting findings exist in theliterature on the association between eNOS gene polymorphism and SCD; there is no data on this association between SCD complications such as vaso-occlusive crisis (VOC), leg ulcers and Priapism in Ghana. Aim The aim of this study was to determine the association between eNOS gene polymorphism, endothelial dysfunction, angiogenesis and the complications of HbSS in Ghanaian SCD patients. Methodology This was a case control study involving 694 subjects, haematological analyses was done for all the subjects. In addition to haematological analysis, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, Angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), Vascular endothelial growth factor (VEGF), NO and genotyping were determined for 213 subjects which included 153 SCD patients with 135 HbSS (46 steady state, 57 VOC, 21 leg ulcers, 11 priapism) and 18 HbSC patients in VOC and 60 age -matched healthy controls (HbAA) who were voluntary blood donors recruited from the Center for Clinical Genetics and Accra Area Blood Centre respectively all at the Korle-Bu Teaching Hospital, Accra. Genotypic analysis of two functionally significant eNOS variants (T786C) polymorphism in the promoter region and the variable number of tandem repeats (VNTR) in intron 4 were carried out with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Plasma concentrations of VCAM-1, ICAM-1, and E-selectin were measured using commercial enzyme immunoassay kits (GenWay, Califonia, USA). Ang-1, Ang-2, and VEGFwere measured by enzyme-linked immunosorbent assay (ELISA) (R&D Systems, UK) and NO using Griess reagent system by ELISA method (Promega, Madison, USA). Results The results showed that there were significantly lower plasma NO levels in the SCD complications as compared to SCD asymptomatic patients and control groups (P<0.001). The results showed that SCD patients had significantlyhigher frequencies of mutant alleles of the eNOS gene polymorphisms (p<0.001). Furthermore, there was a significantly strong positive association between both TCandCC genotypes (OR, 10.33; 95% CI, 1.24-86.06) and (OR, 10.38; 95%CI, 1.781-60.47) respectively of the T786C polymorphism of the eNOS gene in SCD patientswith leg ulcer. Ang-1, Ang-2 and VEGF levels were significantly elevated in SCD patients as compared with controls (P<0.001) and were much higher in patients with complications. Ang-2/Ang-1 ratio was high in SCD patients and still higherin SCD complications. The VCAM-1, ICAM-1, and E-selectin were significantly higher in SCD patients and much higher in those with complications.