Combined effects of cigarette smoking, alcohol drinking and eNOS Glu298Asp polymorphism on blood pressure in Chinese male hypertensive subjects
Zhe Hong 1
Liying Pan 2
Zhangqing Ma 3
Yue Zhu 3
More details
Hide details
Tongji Hospital of Tongji University School of Medicine, Shanghai, China
The First Affiliated Hospital of Wannan Medical College, Wuhu, China
Laboratory of Quantitative Pharmacology, Wannan Medical College, Wuhu, China
Zongyuan Hong   

Laboratory of Quantitative Pharmacology, Wannan Medical College, No. 22, Wenchang West Road, Wuhu 241002, Anhui, China
Publish date: 2019-08-02
Tob. Induc. Dis. 2019;17(August):59
Genetic factors and lifestyle exposures, as well as their combinations, play important roles in the development of hypertension. We examined whether cigarette smoking, alcohol drinking and the Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene generate combined effects on blood pressure (BP) in hypertensive subjects.

A total of 342 essential hypertensive subjects were recruited from Susong community in Anhui province, China, from July 2017 to January 2018, and the plasma biochemical parameters and the genotype on Glu298Asp polymorphism were determined.

There were no gender differences in the distributions of alleles and genotypes in hypertensive subjects. The proportions of cigarette smoking and alcohol drinking in male hypertensive subjects were remarkably higher than those in the females (p<0.001). The systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels of mutant genotypes (Glu/Asp and Asp/Asp) were significantly higher than those of wild genotype (Glu/Glu) (p=0.013 and 0.026, respectively) in male hypertensive subjects. Moreover, the SBP and DBP levels of the mutant genotype were remarkably higher than those of wild genotype in both cigarette smoking and alcohol drinking male hypertensive subjects (p=0.034 and 0.043, respectively).

Cigarette smoking, alcohol drinking and the Glu298Asp polymorphism of the eNOS gene generate combined effects that increase the susceptibility of the mutant genotype to BP in Chinese male hypertensive subjects.

ANCOVA: analysis of covariance, BMI: body mass index, CI: confidence interval, CHOL: total cholesterol, DBP: diastolic blood pressure, eNOS: endothelial nitric oxide synthase, EH: essential hypertension, HDL: high-density lipoprotein, LDL: low-density lipoprotein, NO: nitric oxide, OR: odds ratio, SD: standard deviation, SE: standard error, SBP: systolic blood pressure, TG: total triglyceride
We are indebted to the patients who participated in the study and to their families.
The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none was reported.
This study was supported in part by grants-in-aid from the National Natural Science Foundation of China (proposal number 81671318 and 81171255), the Key Project of Chinese Ministry of Education (proposal number 208058) and the Programs for Science and Technology Development of Anhui Province (proposal number 1501041157).
Z.H., Z.M., Y.Z. and L.P. acquired the data and performed statistical analyses. Z.H. drafted the manuscript. Z.H. and Z.H. conceived the study, participated in its design and coordination, and revised the manuscript for important intellectual content. All authors contributed to the study design and data interpretation, and read and approved the final manuscript.
Not commissioned; externally peer reviewed.
Oliveras A, de la Sierra A. Resistant hypertension: patient characteristics, risk factors, co-morbidities and outcomes. J Hum Hypertens. 2014;28(4):213-217. doi:10.1038/jhh.2013.77.
Fan S, Yang B, Zhi X, et al. Interactions of Methylenetetrahydrofolate Reductase C677T Polymorphism with Environmental Factors on Hypertension Susceptibility. Int J Environ Res Public Health. 2016;13(6). doi:10.3390/ijerph13060601.
Berkin KE, Ball SG. Essential hypertension: the heart and hypertension. Heart. 2001;86(4):467-475. doi:10.1136/heart.86.4.467.
Messerli FH, Williams B, Ritz E. Essential hypertension. Lancet. 2007;370(9587):591-603. doi:10.1016/S0140-6736(07)61299-9.
Bolivar JJ. Essential hypertension: an approach to its etiology and neurogenic pathophysiology. Int J Hypertens. 2013;2013:547809. doi:10.1155/2013/547809.
Gamil S, Erdmann J, Abdalrahman IB, Mohamed A. Association of NOS3 gene polymorphisms with essential hypertension in Sudanese patients: a case control study. BMC Med Genet. 2017;18(1):128. doi:10.1186/s12881-017-0491-7.
Frazer KA, Murray SS, Schork NJ, Topol EJ. Human genetic variation and its contribution to complex traits. Nat Rev Genet. 2009;10(4):241-251. doi:10.1038/nrg2554.
Poulter NR, Prabhakaran D, Caulfield M. Hypertension. Lancet. 2015;386(9995):801-812. doi:10.1016/S0140-6736(14)61468-9.
Sung YJ, de Las Fuentes L, Schwander KL, Simino J, Rao DC. Gene-smoking interactions identify several novel blood pressure loci in the Framingham Heart Study. Am J Hypertens. 2015;28(3):343-354. doi:10.1093/ajh/hpu149.
Cooke JP, Dzau VJ. Nitric oxide synthase: role in the genesis of vascular disease. Annu Rev Med. 1997;48:489-509. doi:10.1146/
Yamamoto T, Kimura T, Ota K, et al. Effects of a nitric oxide synthase inhibitor on vasopressin and atrial natriuretic hormone release, thermogenesis and cardiovascular functions in response to interleukin-1 beta in rats. Tohoku J Exp Med. 1994;174(1):59-69. doi:10.1620/tjem.174.59.
Cardillo C, Panza JA. Impaired endothelial regulation of vascular tone in patients with systemic arterial hypertension. Vasc Med. 1998;3(2):138-144. doi:10.1177/1358836X9800300208.
Huang PL, Huang Z, Mashimo H, et al. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature. 1995;377(6546):239-242. doi:10.1038/377239a0.
Lin KF, Chao L, Chao J. Prolonged reduction of high blood pressure with human nitric oxide synthase gene delivery. Hypertension. 1997;30(3):307-313. doi:10.1161/01.hyp.30.3.307.
Wattanapitayakul SK, Mihm MJ, Young AP, Bauer J. Therapeutic implications of human endothelial nitric oxide synthase gene polymorphism. Trends Pharmacol Sci. 2001;22(7):361-368. doi:10.1016/S0165-6147(00)01692-8.
Li YY. Endothelial Nitric Oxide Synthase G894T Gene Polymorphism and Essential Hypertension in the Chinese Population: a Meta-Analysis Involving 11,248 Subjects. Intern Med. 2011;50:2099-2106. doi:10.2169/internalmedicine.50.5856.
Yang B, Xu JR, Liu XM, et al. Polymorphisms of rs1799983 (G>T) and rs1800780 (A>G) of the eNOS gene associated with susceptibility to essential hypertension in the Chinese Hui ethnic population. Genet Mol Res. 2013;12(3):3821-3829. doi:10.4238/2013.March.26.2.
Takaoka K, Yoshimura M, Ogawa H, et al. Comparison of the risk factors for coronary artery spasm with those for organic stenosis in a Japanese population: role of cigarette smoking. Int J Cardiol. 2000;72(2):121-126. doi:10.1016/S0167-5273(99)00172-2.
Wang XL, Sim AS, Wang MX, Murrell G, Trudinger B, Wang J. Genotype dependent and cigarette specific effects on endothelial nitric oxide synthase gene expression and enzyme activity. FEBS Lett. 2000;471(1):45-50. doi:10.1016/S0014-5793(00)01356-9.
Hong SW, Linton JA, Shim JY, Lee HR, Kang HT. Association of alcohol consumption pattern with risk of hypertension in Korean adults based on the 2010-2012 KNHANES. Alcohol. 2016;54:17-22. doi:10.1016/j.alcohol.2016.05.006.
Hayibor LA, Zhang J, Duncan A. Association of binge drinking in adolescence and early adulthood with high blood pressure: findings from the National Longitudinal Study of Adolescent to Adult Health (1994-2008). J Epidemiol Community Health. 2019;73. doi:10.1136/jech-2018-211594.
Kimani S, Mirie W, Chege M, Okube O, Muniu S. Association of lifestyle modification and pharmacological adherence on blood pressure control among patients with hypertension at Kenyatta National Hospital, Kenya: a cross-sectional study. BMJ Open. 2019;9(1):e023995. doi:10.1136/bmjopen-2018-023995.
Arkwright PD, Beilin LJ, Rouse I, Armstrong BK, Vandongen R. Effects of alcohol use and other aspects of lifestyle on blood pressure levels and prevalence of hypertension in a working population. Circulation. 1982;66(1):60-66. doi:10.1161/01.cir.66.1.60.
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. doi:10.1161/01.hyp.32.1.3.
Cooke JP. Role of nitric oxide in progression and regression of atherosclerosis. West J Med. 1996;164(5):419-424.
Philip I, Plantefeve G, Vuillaumier-Barrot S, et al. G894T polymorphism in the endothelial nitric oxide synthase gene is associated with an enhanced vascular responsiveness to phenylephrine. Circulation. 1999;99(24):3096-3098. doi:10.1161/01.cir.99.24.3096.
Raman CS, Li H, Martasek P, Král V, Masters B, Poulos T. Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center. Cell. 1998;95(7):939-950. doi:10.1016/S0092-8674(00)81718-3.
Fischmann TO, Hruza A, Niu XD, et al. Structural characterization of nitric oxide synthase isoforms reveals striking active-site conservation. Nat Struct Biol. 1999;6(3):233-242. doi:10.1038/6675.
Kone BC. Protein-protein interactions controlling nitric oxide synthases. Acta Physiol Scand. 2000;168(1):27-31. doi:10.1046/j.1365-201x.2000.00629.x.
Li YY. Endothelial nitric oxide synthase G894T gene polymorphism and essential hypertension in the Chinese population: a meta-analysis involving 11,248 subjects. Intern Med. 2011; 50(19):2099-2106. doi:10.2169/internalmedicine.50.5856.
van Leer EM, Seidell JC, Kromhout D. Differences in the association between alcohol consumption and blood pressure by age, gender, and smoking. Epidemiology. 1994;5(6):576-582. doi:10.1097/00001648-199411000-00004.
Kugiyama K, Yasue H, Ohgushi M, et al. Deficiency in nitric oxide bioactivity in epicardial coronary arteries of cigarette smokers. J Am Coll Cardiol. 1996;28(5):1161-1167. doi:10.1016/S0735-1097(96)00325-7.
Ota Y, Kugiyama K, Sugiyama S, et al. Impairment of endothelium-dependent relaxation of rabbit aortas by cigarette smoke extract--role of free radicals and attenuation by captopril. Atherosclerosis. 1997;131(2):195-202. doi:10.1016/S0021-9150(97)06106-6.
Puddey IB, Beilin LJ, Vandongen R, Rouse IL, Rogers P. Evidence for a direct effect of alcohol consumption on blood pressure in normotensive men. A randomized controlled trial. Hypertension. 1985;7(5):707-713. doi:10.1161/01.hyp.7.5.707.
Wallace RB, Lynch CF, Pomrehn PR, Criqui MH, Heiss G. Alcohol and hypertension: epidemiologic and experimental considerations. The Lipid Research Clinics Program. Circulation. 1981;64(3 Pt 2):III 41-47.