Association between -786TC polymorphism in the endothelial nitric oxide synthase gene and hypertension in the Tunisian population Riadh Jemaa ⁎, Amani Kallel, Yousra Sediri, Souheil Omar, Moncef Feki, Monia Elasmi, Samah Haj-Taieb, Haïfa Sanhaji, Naziha Kaabachi Research Laboratory LR99ES11, Department of Biochemistry, Rabta University Hospital, Tunis, Tunisia abstract article info Article history: Received 11 August 2010 Available online 29 December 2010 Keywords: NOS3 gene polymorphism Hypertension Nitric oxide Background: Nitric oxide (NO) is produced by endothelial cells and serves as a potent vasodilator. Several lines of evidence have shown that NO plays an important role in the regulation of blood pressure and regional blood flow. Recent genetic studies have shown an association between the -786TC polymorphism in the endothelial nitric oxide synthase gene (NOS3) and coronary artery diseases, but any possible association with hypertension has been controversial. In the present study, we examined a possible association between the -786TC polymorphism of the NOS3 gene and hypertension in a sample of the Tunisian population. Methods: A total of 288 unrelated Tunisian patients with hypertension and 373 normotensive subjects were included in the study. The -786TC gene polymorphism was analyzed by PCR-RFLP. Results: A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with hypertension had a frequency of 19.7% for CC genotype, 52.9% for TC genotype and 27.3% for TT genotype. The control had a frequency of 14.7% for the CC genotype, 47.2% for the TC genotype and 38.1% for the TT genotype (χ² = 9.09, p = 0.01). The hypertension patient group showed a significant higher frequency of the C allele compared to the controls (0.46 vs. 0.38; χ² = 8.26, p = 0.004). The odds ratio of hypertension for C vs. T allele frequencies was statistically significant 1.59 (1.14–2.21) at 95% CI, p = 0.004 in men, whereas it was non-significant in women 1.21 (0.87–1.67), p=0.23. Conclusion: The present study showed a significant and independent association between the -786TC gene polymorphism (presence of C allele) and hypertension in the Tunisian population. © 2010 Elsevier Inc. All rights reserved. Introduction Hypertension is a multifactorial disease with genetic and environ- mental components. Clinical and animal studies have suggested that an alteration in nitric oxide (NO) metabolism may be a contributing factor in the pathogenesis of hypertension (Ignarro et al., 1987; Hung et al., 1995; Hyndman et al., 2002). NO a potent vasodilator produced by endothelial cells, plays a prominent role in regulating blood pressure (BP), and many lines of evidence suggest correlations between various genetic polymor- phisms of the endothelial nitric oxide synthase (eNOS) gene (NOS3) and cardiovascular diseases (Wang et al., 1996; Ichihara et al., 1998; Hingorani et al., 1999; Hibi et al., 1998; Yoshimura et al., 1998, 2000; Ghilardi et al., 2002; Ogawa et al., 1999; Takaoka, 2004). Three clinically relevant polymorphisms in this gene have been commonly studied: a single nucleotide polymorphism (SNP) in the promoter region (-786TC), a SNP in exon 7 that results in an amino acid change in protein (Glu298Asp), and the variable number of tandem repeats (VNTR) in intron 4 (Hingorani, 2001; Tanus-Santos et al., 2001). Importantly, inconsistent associations between these NOS3 genetic variations and hypertension have been found. While some studies showed significant association with hypertension (Hyndman et al., 2002; Miyamoto et al., 1998; Shoji et al., 2000; Uwabo et al., 1998; Jachymova et al., 2001), other studies described lack of such association (Benjafield and Morris, 2000; Karvonen et al., 2002; Tsujita et al., 2001). We have recently shown that the 27-bp tandem repeats in intron 4 of the NOS3 gene was a significant determinant of development of myocardial infarction (Jemaa et al., 2007) and hypertension in the Tunisian population (Jemaa et al., 2009). Conflicting reports have been published on the relationship between the -786TC polymorphism in the NOS3 gene and hypertension (Hyndman et al., 2002; Kajiyama et al., 2000). Considering the contradictory results, the aim of the present study was to investigate the possible association between the -786TC polymorphism of the NOS3 gene and hypertension in a sample of the Tunisian population. Materials and methods Subjects A total of 661 unrelated individuals were included in the study. They consisted of 288 hypertensive patients (120 men and 168 women) and Experimental and Molecular Pathology 90 (2011) 210–214 ⁎ Corresponding author. Laboratoire de Biochimie, Hôpital la Rabta, 1007, Jabbari, Tunis, Tunisia. Fax: +216 71 561 912. E-mail address: jemaa_riadh@yahoo.fr (R. Jemaa). 0014-4800/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yexmp.2010.12.006 Contents lists available at ScienceDirect Experimental and Molecular Pathology journal homepage: www.elsevier.com/locate/yexmp