Association of NOS3 gene polymorphisms with essential hypertension in Sudanese patients: a case control study

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.Electronic supplementary materialThe online version of this article (10.1186/s12881-017-0491-7) contains supplementary material, which is available to authorized users.

Research Article Glu298Asp polymorphism in the <i>NOS3</i> gene is not associated with susceptibility to chronic heart failure in a Russian population

“…Contradictory results have been obtained in other studies on a possible correlation between the eNOS Glu298Asp polymorphism and heart disease (Hibi et al, 1998;Miyamoto et al, 1998;Kato et al, 1999;Nassar et al, 2001;Colombo et al, 2003;Shaw et al, 2005;van Beynum et al, 2008;Velloso et al, 2010;Gamil et al, 2017;Khatami et al, 2017;Shahid and Rehman, 2017). This may depend on group selection, due to variable distribution of the polymorphism in different ethnic groups, and small sample size (Chen et al, 2001;Rosas-Vargas et al, 2003;Sandrim et al, 2006).…”

“…The polymorphism does not change the kinetics of the reaction leading to the production of NO, although eNOS Asp298 has been found more susceptible to proteolytic cleavage than eNOS Glu298, and subjects with the Asp298 variant may show a reduction in nitric oxide production ( Tesauro et al, 2000;Leeson et al, 2002). The eNOS Glu298Asp (rs1799983) polymorphism has been implicated as a risk factor for various cardiovascular diseases, such as congenital heart defects ( Shaw et al, 2005;Van Beynum et al, 2008;Khatami et al, 2017), coronary artery disease (Colombo et al, 2003;Shahid and Rehman, 2017), myocardial infarction (Hibi et al, 1998), hypertension (Miyamoto et al, 1998;Gamil et al, 2017) and heart failure (Velloso et al, 2010). However, other authors report contradictory results (Kato et al, 1999;Nassar et al, 2001;Gamil et al, 2017).…”

Features of clinical and laboratory indicators in alcoholic liver disease in combination with arterial hypertension depending on T786C polymorphism of the eNOS gene

“…Зниження базаль-ної продукції NO може призводити до розвитку АГ, тромбозу та вазоспазму. Багатьма дослідженнями в різних популяціях показана асоціація розвитку АГ із поліморфізмом гена eNOS, зокрема із T786C [8,9,10,11]. З іншого боку, доведена потенційна роль NO в абдомінальній гемодинаміці при захворюваннях печінки.…”

Association between NOS3 polymorphisms and osteonecrosis of the femoral head

“…The dysregulation of eNOS increases vascular tension, which damages angiogenesis ability, increases blood clots risk, and reduces bone mineral density [14]. NOS3 gene polymorphisms show close associations with several diseases caused by vascular lesions, such as acute myocardial infarction, essential hypertension, coronary heart disease and avascular necrosis of femoral head [15][16][17][18].…”