Association between eNOS Gene Polymorphism (T786C and VNTR) and Sickle Cell Disease Patients in Ghana.

Ivy Ekem,Eric Donkor,Kate Otu,Fredericka Sey,Daniel Achel,John Ahenkorah,William Kudzi,Alfred Doku,Gifty Boatemaa,Campbell Dale,Charles Antwi-Boasiako,Bartholomew Dzudzor,Elvis Aboagye

doi:10.3390/diseases6040090

Abstract

Endothelial nitric oxide synthase (eNOS) variants have been found to be associated with several vascular disorders as well as the pathogenesis of sickle cell disease (SCD) complications such as vaso-occlusive crises (VOC). Studies on eNOS gene variants among SCD patients are rare in Ghana and several other African countries. The current study aimed to determine a possible association between variants of the eNOS gene (variable number of tandem repeats in intron 4 and T786C) in SCD complications among Ghanaian patients. This was a cross-sectional study involving 89 HbSS patients with complications and 46 HbSS patients without complications. Genomic DNA was extracted from leukocytes in the buffy coat and separated from collected whole blood samples of the study participants. PCR amplification, followed by restriction fragment length polymorphism (RFLP) was used to genotype T786C (rs2070744) variants. Variable number of tandem repeats (VNTR) in intron 4 was genotyped by PCR and direct electrophoresis. There was a significant difference in the genotype frequency of the T786C variant between HbSS patients with complications and those without complications (p = 0.0165). However, there was no significant difference in the VNTR intron 4 variant of the eNOS gene between patients with complications and those without complications (p > 0.05). The study shows an association between the eNOS gene variant (T786C) and complications in SCD.

Highlights

Sickle cell disease (SCD) patients constitute 1% of the global population, and over 75% of this percentage is found in sub-Saharan Africa [1,2]
Another study conducted in Africa, reported that endothelial nitric oxide synthase (eNOS) variants are less frequent in sickle cell disease (SCD) patients and that they lack any functional significance among these patients [23]
Findings from these studies suggest that the possible association between eNOS gene variants and SCD seem to be related to ethnogenomic diversity, among other factors

Summary

Introduction

Sickle cell disease (SCD) patients constitute 1% of the global population, and over 75% of this percentage is found in sub-Saharan Africa [1,2]. In Ghana, the incidence of SCD is about 2% of all births per year [3]. It is a major genetic disease associated with increased mortality in Ghana [4]. Soluble endothelial cell adhesion molecules (ICAM-1, VCAM-1, and E-selectin) play a vital physiological role in the recruitment and binding of inflammatory cells to vascular endothelium, in venules [8]. The expression of these molecules has been found to be modulated by endothelial nitric oxide (NO) produced by the endothelial nitric oxide synthase (eNOS) gene

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Discussion

Conclusion