Combinations of NOS3 and CYBA alleles and essential hypertension risk in men
Abstract
Aim. To study the role of Glu298Asp and C242T point substitutions and their combinations in the development of essential arterial hypertension (AH). Material and methods. The study included 511 men aged 19—61 years (mean age 36,2±5,5 years): 409 patients with confirmed AH diagnosis (main group, MG), and 102 healthy men without cardiovascular disease (control group, CG). Alleles of interest were identified using polymerase chain reaction and restriction fragment length analysis. Results. Among AH patients, the prevalence of mutant allele 298Asp was 22,8 %, vs. 24,2 % in the CG (р>0,05). The prevalence of mutant allele 242Т was 31,8 % and 37,8 % in MG and CG, respectively (p>0,05). The combinations where mutant allele 298Asp outnumbered mutant allele 242Т were shown to increase AH risk. In the binary logistic regression model, AH odds ratio and confidence intervals were calculated. The p value of the model was assessed with maximal likelihood test. In people with “prevalent” NOS3 mutation, AH risk was higher (OR 1,55; 95 %CI 1,00—2,40; p=0,049). Adverse genotypes included 298Het/242Wt; 298Mut/242Het; 298Mut/242Wt и 298Wt/242Het. Conclusion. Point mutations of Glu298Asp and C242T did not increase AH risk in men substantially. However, other genotype combinations, associated with increased AH risk, were identified.
About the Authors
P. I. MakarevichRussian Federation
E. Yu. Andreenko
Russian Federation
A. V. Balatsky
Russian Federation
A. V. Kolotvin
Russian Federation
N. O. Popova
Russian Federation
E. B. Yarovaya
Russian Federation
L. M. Samokhodskaya
Russian Federation
V. A. Tkachuk
Russian Federation
References
1. Leusen JH, Verhoeven AJ, Roos D. Interactions between the components of the human NADPH oxidase: intrigues in the phox family. J Lab Clin Med 1996; 128(5): 461—76.
2. Schulz E, Jansen T, Wenzel P, et al. Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction in hypertension. Antioxid Redox Signal 2008; 10(6): 1115—26.
3. Channon KM, Guzik TJ. Mechanisms of superoxide production in human blood vessels: relationship to endothelial dysfunction, clinical and genetic risk factors. J Physiol Pharmacol 2002; 53(4 Pt 1): 515—24.
4. Л. Ю. Каминская. А. А. Жлоба, Л. А. Александрова и др. Влияние донатора NO нитрозотиола глутатиона на уровень окислов азота и малонового диальдегида в крови крыс. Артер гиперт 2005; 11(1): 10—7.
5. Ghazali DM, Rehman A, Rahman AR. Candidate gene polymorphisms and their association with hypertension in Malays. Clin Chim Acta 2008; 388(1—2): 46—50.
6. Srivastava K, Narang R, Sreenivas, et al. Association of eNOS Glu298Asp gene polymorphism with essential hypertension in Asian Indians. Clin Chim Acta 2008; 387(1—2): 80—3.
7. Godfrey V, Chan SL, Cassidy A, et al. The functional consequence of the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene in young healthy volunteers. Cardiovasc Drug Rev 2007; 25(3): 280—8.
8. Di Castelnuovo A, Soccio M, Iacoviello L, et al. The C242T polymorphism of the p22phox component of NAD (P) H oxidase and vascular risk. Two case-control studies and a metaanalysis. Thromb Haemost 2008; 99(3): 594—601.
9. Moreno MU, San José G, Fortuño A, et al. The C242T CYBA polymorphism of NADPH oxidase is associated with essential hypertension. J Hypertens 2006; 24(7): 1299—306.
10. Krex D, Ziegler A, König IR, et al. Polymorphisms of the NADPH oxidase P22PHOX gene in a Caucasian population with intracranial aneurysms. Cerebrovasc Dis 2003; 16(4): 363—8.
11. Ito D, Murata M, Watanabe K, et al.C242T polymorphism of NADPH oxidase p22 PHOX gene and ischemic cerebrovascular disease in the Japanese population. Stroke 2000; 31(4): 936—9.
12. Wolff B, Grabe HJ, Schlüter C, et al. Endothelial nitric oxide synthase Glu298Asp gene polymorphism, blood pressure and hypertension in a general population sample. J Hypertens 2005; 23(7): 1361—6.
13. Karvonen J, Kauma H, Kervinen K, et al. Endothelial nitric oxide synthase gene Glu298Asp polymorphism and blood pressure, left ventricular mass and carotid artery atherosclerosis in a population-based cohort. J Intern Med 2002; 251(2): 102—10.
14. Arca M, Conti B, Montali A, et al. C242T polymorphism of NADPH oxidase p22phox and recurrence of cardiovascular events in coronary artery disease. Arterioscler Thromb Vasc Biol 2008; 28(4): 752—7.
Review
For citations:
Makarevich P.I., Andreenko E.Yu., Balatsky A.V., Kolotvin A.V., Popova N.O., Yarovaya E.B., Samokhodskaya L.M., Tkachuk V.A. Combinations of NOS3 and CYBA alleles and essential hypertension risk in men. Cardiovascular Therapy and Prevention. 2010;9(3):4-9. (In Russ.)