Abstract
BackgroundEssential hypertension (EH) is influenced by various environmental and genetic factors. Nitric oxide is important for the functional integrity of the vascular endothelium and is produced in endothelial cells by the enzyme endothelial nitric oxide synthase (eNOS). EH has a strong genetic component, and the NOS3 gene, which encodes eNOS, represents an interesting candidate for contribution to the phenotype. The most clinically relevant polymorphisms in the NOS3 gene are rs1799983 in exon 7 (encoding Glu298Asp), a variable number tandem repeat (VNTR) in intron 4, and rs2070744 (T-786C) in the promoter region. This study aims to investigate the association between these three polymorphisms in the NOS3 gene and EH in Sudanese patients.MethodsHypertensive patients (n = 157) > 18 years of age with established hypertension from various hospitals in Khartoum, and controls (n = 85) > 18 years of age and with blood pressure measurements <140/90, were included in this case control study. Genotypes at the NOS3 variants were determined using TaqMan and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analyses. Genotype and allele frequencies were compared between the two groups by χ2 analysis, and differences were expressed as odds ratios with 95% confidence intervals (CIs). P values <0.05 were considered statistically significant.ResultsThe rs2070744 polymorphism in NOS3 was found to be associated with EH in the Sudanese population as the patients group had higher frequency of CC genotype compared with the controls (6.6% vs 6.1%, p = 0.02). Considering a dominant inheritance model, the frequency of TC + CC genotypes in patients was significantly higher than that in the control subjects (52.6% vs 34.1%, respectively; p < 0.01), with an odds ratio (95% CI) of 2.14 (1.23–3.74). In addition, the C allele was more frequent in the patients than the control group (29.6% vs 20%, p = 0.03, OR = 1.84 (1.15–2.93)). The c allele of intron 4 VNTR was reported in >1% of the Sudanese population under study.ConclusionThe results of this study indicated that the rs2070744 polymorphism in NOS3 may be a genetic susceptibility factor for EH in the Sudanese population. The c allele of intron 4 VNTR is not rare in the Sudanese population.
Highlights
Essential hypertension (EH) is influenced by various environmental and genetic factors
Associations between genotypes and general characteristics of the study sample We studied the associations between the three polymorphisms and the clinical characteristics of the study sample stratified according to age, gender, Body mass index (BMI), systolic and diastolic blood pressure (BP), smoking, and presence of additional complications alongside hypertension
We found that all three included Endothelial nitric oxide synthase gene (NOS3) polymorphisms are in linkage disequilibrium, and that this effect was strongest between rs1799983 and the variable number tandem repeat (VNTR) in intron 4, which is expected as they are in close physical proximity to one another
Summary
Essential hypertension (EH) is influenced by various environmental and genetic factors. Nitric oxide is important for the functional integrity of the vascular endothelium and is produced in endothelial cells by the enzyme endothelial nitric oxide synthase (eNOS). EH has a strong genetic component, and the NOS3 gene, which encodes eNOS, represents an interesting candidate for contribution to the phenotype. Essential hypertension (EH) is a multifactorial disease caused by various environmental and genetic factors. The prevalence of Hypertension continues to rise despite recent advances in diagnosis and treatment. 40% of the global adult population aged 25 and above suffer from hypertension [2]. In Sudan, the prevalence of hypertension was reported as 20% in 2011 [3]. Hypertension is a major contributor to the growing global pandemic of CVD and stroke. Nitric oxide (NO) is important for the anatomical and functional integrity of the vascular endothelium, which
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