GENE POLYMORPHISMS WITH ESSENTIAL HYPERTENSIONadmin
ASSOCIATION OF NOS3 GENE POLYMORPHISMS WITH ESSENTIAL HYPERTENSION IN SUDANESE PATIENTS: A CASE-CONTROL STUDY
Sahar Gamil1, Jeanette Erdmann2,3,4 , Ihab B Abdalrahman5 , Abdelrahim O. Mohamed1,6
¹Department of Biochemistry, Faculty of Medicine, University of Khartoum, P.O. Box: 102, Khartoum, Sudan.
2Institute for Cardiogenetics, University of Lübeck, 23562 Lübeck, Germany
3DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, 23562 Lübeck, Germany
4University Heart Center Luebeck, 23562 Lübeck, Germany
5Department of Medicine, Faculty of Medicine, University of Khartoum, P.O. Box: 102, Khartoum, Sudan
6Neelain Institute for Medical Research, Al-Neelain University, Khartoum, Sudan
Email adresses: Sahar Gamil (firstname.lastname@example.org), Jeanette Erdmann (email@example.com), Ihab B Abdalrahman (firstname.lastname@example.org), Abdelrahim O. Mohamed (email@example.com ).
Corresponding author: Sahar Gamil
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). Essential Hypertension (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.
Hypertensive patients (n = 157) with established hypertension and controls (n = 85) 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.
The CC genotype of the rs2070744 polymorphism in NOS3 was found to be of higher frequency in patients 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 results of this study indicated that the rs2070744 polymorphism in NOS3 may be a genetic susceptibility factor for EH in the Sudanese population.