Endothelial Nitric Oxide Synthase 3 (eNOS3) Gene Polymorphisms and Essential Hypertension in Javanese Ethnic Group


  • Fitranto Arjadi Jenderal Soedirman University
  • Saefuddin Aziz Jenderal Soedirman University
  • Alfi Muntafiah Jenderal Soedirman University




Hypertension is still a major public health problem in Indonesia and in several other countries. This disease is caused by multi factorial components involving both environmental and genetic factors. eNOS3 gene is one of the enzymes related to the high prevalence of hypertension. This gene expresses the NOS enzyme which regulates the synthesis of NO. NOS enzyme causes vasodilatation which decreases peripheral resistance and lowers blood pressure. This cross sectional study compared hypertension patients to those with normal blood pressure in the age group of 40-80 years old. The main purpose of this study is to evaluate the influence of eNOS3 gene Glu298Asp allele expression in Javanese ethnic group patients with hypertension. The samples consist of 50 respondents with hypertension and 50 respondents with normotension as control. Data of eNOS3 gene polymorphisms and NO plasma levels from the respondents were analyzed using t-test and chi-square test. Glu298Asp allele genotype variation in eNOS3 gene was detected by PCR-FRLP using primers G894TF and G894TR and the PCR products were cut using Mbol restriction enzymes. Sequencing result of each polymorphism band shows a typical nucleotide sequence compared to the nucleotide sequence of eNOS3 gene in Gen Bank. The results of this study showed no connection between Glu298Asp allele polymorphism in eNOS3 gene with hypertension in Javanese. There was also no relation between eNOS3 gene polymorphisms with high levels of respondents' NO plasma. Average NO plasma level of hypertension patients is 34,53 µmol/L, whereas average NO level of normal blood pressure is 32,5 µmol/L.

Keywords: Allele Glu298Asp, eNOS3 gene, G894T, hypertension, Javanese ethnic, NO plasma level



Download data is not yet available.

Author Biographies

Fitranto Arjadi, Jenderal Soedirman University

Fakultas Kedoketeran dan Ilmu-ilmu Kesehatan

Saefuddin Aziz, Jenderal Soedirman University

Fakultas Biologi

Alfi Muntafiah, Jenderal Soedirman University

Fakultas Kedoketeran dan Ilmu-ilmu Kesehatan


Badan Penelitian dan Pengembangan Kesehatan Departemen Kesehatan Republik Indonesia. Riset Kesehatan Dasar. Jakarta: Badan Penelitian dan Pengembangan Kesehatan Departemen Kesehatan Republik Indonesia; 2007.

Dosh SA. The Treatment of Adults with Essential Hypertension. The Journal of Family Practice. 2002; 51(1): 74-80.

Wang HG, Wang JL, Chang P, et al. Endothelial Nitric Oxide Synthase Gene Polymorphisms and Essential Hypertension in Han Chinese. Genetic and Molecular Research. 2010; 9(3): 1896-1907.

Kingah PL, Luu HN, Volcik KA, Morrison AC, Nettleton JA, and Boerwinkle E. Association of NOS3 Glu298Asp SNP with Hypertension and Possible Effect Modification of Dietary Fat Intake in the ARIC Study. Hypertension Research. 2010; 33(2): 165–169.

Tsutsui M, Shimokawa H, Otsuji Y, Ueta Y, Sasaguri Y, and Yanagihara N. Nitric Oxide Synthases and Cardiovascular Diseases: Insights from Genetically Modified Mice. Circulation Journal. 2009; 73(6): 986-993.

Pyle RL, Abbott J, and MacLean H. Pulmonary Hypertension and Cardiovascular Sequelae in 54 Dogs. International Journal of Applied Research in Veterinary Medicine. 2004; 2(2): 99-109.

Kimura L, Angeli CB, Auricchio MTBM, et al. Multilocus Family-Based Association Analysis of Seven Candidate Polymorphisms with Essential Hypertension in an African-Derived Semi-Isolated Brazilian Population. International Journal of Hypertension. 2012; 2012: 8.

Pacanowski MA, Zineh I, Cooper-DeHoff RM, Pepine CJ, and Johnson JA. Genetic and Pharmacogenetic Associations between NOS3 Polymorphisms, Blood Pressure, and Cardiovascular Events in Hypertension. American Journal of Hypertension. 2009; 22(7): 748–753.

Cruz-González I, Corral E, Sánchez-Ledesma M, Sánchez-Rodríguez A, Martín-Luengo C, and González-Sarmiento R. Association between -T786C NOS3 Polymorphism and Resistant Hypertension: A Prospective Cohort Study. BMC Cardiovascular Disorders. 2009; 9: 35-42.

Wang P, Koehle MS, and Rupert JL. Genotype at the Missense G894T Polymorphism (Glu298Asp) in the NOS3 Gene is Associated with Susceptibility to Acute Mountain Sickness. High Altitude Medicine and Biology. 2009; 10(3): 261-267.

Mehmetoğlu I, Yilmaz G, Kurban S, Acar H, and Düzenli MA. Investigation of Enos Gene Intron 4 A/B VNTR and Intron 23 Polymorphisms in Patients with Essential Hypertension. Turkish Journal of Medical Sciences. 2010; 40(3): 479-484.

Shankarishan P, Borah PK, Ahmed G, and Mahanta J. Prevalence of Endothelial Nitric Oxide Synthase (Enos) Gene Exon 7 Glu298Asp Variant in North Eastern India. Indian Journal of Medical Research. 2011; 133(5): 487-491.

Miyamoto Y, Saito Y, Kajiyama N, et al. Endothelial Nitric Oxide Synthase Gene is Positively Associated with Essential Hypertension. Hypertension. 1998; 32(1): 3–8.

Yang Y, Du K, Liu Z, and Lu X. Endothelial Nitric Oxide Synthase (eNOS) 4b/a Gene Polymorphisms and Coronary Artery Disease: Evidence from a Meta-Analysis. International Journal of Molecular Science 2014; 15(5): 7987-8003.

Casas JP, Cavalleri GL, Bautista LE, Smeeth L, Humphries SE, and Hingorani AD. Endothelial Nitric Oxide Synthase Gene Polymorphisms and Cardiovascular Disease: A HuGE Review. American Journal of Epidemiology. 2006; 164(10): 921-935.

Ali AAA, Wassim NM, Dowaidar M, and Yaseen AE. Association of eNOS (E298D) and CYP2J2 (−50 G/T) Gene Polymorphisms with Hypertension among Egyptian Cases. The Journal of Basic and Applied Zoology. 2013; 66(4): 234-241.

Ormezzano O, Amar J, Vehier CM, et al. Association of Enos Glu298Asp Gene Polymorphism with Circadian Blood Pressure Rhythm. Journal of Human Hypertension. 2007; 21: 501–503.

Jáchymová M, Horky K, Bultas J, et al. Association of the Glu298Asp Polymorphism in the Endothelial Nitric Oxide Synthase Gene with Essential Hypertension Resistant to Conventional Therapy. Biochemical and Biophysical Research Communication. 2001; 284(2): 426–430.

Sulastri D, Rahmatini, Lipoeto NI, dan Edwar Z. Pengaruh Asupan Antioksidan terhadap Ekspresi Gen eNOS3 pada Penderita Hipertensi Etnik Minangkabau. Majalah Kedokteran Indonesia. 2010; 60(12): 564-570.

Afrasyap L and Osturk G. NO Synthese Gene Polymorphism (Glu 298 Asp) in the Patients with Coronary Arthery Disease from Turki Population. Acta Biochimica et Biophisica Sinicia. 2004; 36(10): 661-666.

Dosenko VE, Zagoriy VY, Haytovich NV, Gordok OA, and Moibenko AA. Allelic Polymorphism of Endothelial NO-Synthase Gene and its Functional Manifestations. Acta Biochimica Polonica. 2006; 53(2): 299–302.

Ferlito S, Gallina M, Pitari GM, and Bianchi A. Nitric Oxide Plasma Levels in Patients with Chronic and Acute Cerebrovascular Disorders. Panminerva Medica. 1998; 40(1): 51–54.

Jeerooburkhan N, Jones LC, Bujac S, et al. Genetic and Environmental Determinants of Plasma Nitric Oxides and Risk of Ischemic Heart Disease. Hypertension, 2001; 38(5): 1054–1061.

Klahr S. The Role of Nitric Oxide in Hypertension and Renal Disease Progression. Nephrology Dialysis Transplantation. 2001: 16(1); 60–62.

Kumar CA and Das UN. Lipid Peroxides, Antioxidants and Nitric Oxides in Patients with Pre-Eclampsia and Essential Hypertension. Medical Science Monitor. 2000; 6(5): 901–907.

Rodríguez-Esparragón FJ, Rodríguez-Pérez JC, Macías-Reyes A, and Alamo-Santana F. Peroxisome Proliferator-Activated Receptor-Gamma2-Pro12Ala and Endothelial Nitric Oxide Synthase-4a/B Gene Polymorphisms are Associated with Essential Hypertension. Journal of Hypertension. 2003: 21(9): 1649–1655.

Gouni-Berthold I, Giannakidou E, Müller-Wieland D, et al. Peroxisome Proliferator-Activated Receptor-[Gamma]2 Pro12Ala and Endothelial Nitric Oxide Synthase-4a/B Gene Polym Orphisms are not Associated with Hypertension in Diabetes Mellitus Type 2. Journal of Hypertension. 2005; 23(2): 301–308.

Zhao Q, Su SY, Chen SF, Li B, and Gu DF. Association Study of the Endothelial Nitric Oxide Synthase Gene Polymorphisms with Essential Hypertension in Northern Han Chinese. Chinese Medical Journal. 2006; 119(113): 1065–1071






Research Article