Association study of NOS3 genetic polymorphism and the efficacy of anti-hypertensive drug treatment on patient with essential hypertension

Abstract

Abstract:

AIM: To evaluate the effect of NOS3 gene polymorphism on anti-hypertensive drug treatment for patient with essential hypertension (EH). METHODS: General information and Clinical biochemical indicators of EH patients taking compound reserpine, hypertension pill and Zhenju hypertension pill were collected. RELP-PCR was used to test the polymorphism of NOS3 gene (rs4496877, rs1808593 and rs3918186).A quantitative trait analysis was performed to evaluate the relation between NOS3 genetic variation and blood pressure taking different anti-hypertensive drugs. RESULTS: Quantitative trait analysis showed significant differences in diastolic blood pressure (DBP) among the genotypes (TT,TG and GG) of rs1808593 in patients taking the hypertension pill after adjusting covariants (P=0.035). Stratification analysis indicated that DBP of male patients taking the hypertension pill significantly decreased with the variation (T＞G) of rs1808593 (P=0.046). For patients (age≥55) taking the hypertension pill, DBP of genotype TT was significantly higher than genotypes TG and GG of rs1808593(P=0.008). CONCLUSION: NOS3 gene rs1808593 mutation might relate to the anti-hypertensive effect of the hypertension pill.

Key words: NOS3 gene, gene polymorphisms, essential hypertension, drug efficacy

CLC Number:

R968

JIN Yuelong, WANG Linhong, ZHU Lijun, LIANG Wei, DUAN Ying, YANG Song, CHEN Yanchun, ZHAO Xianghai, SHEN Chong, YAO Yingshui. Association study of NOS3 genetic polymorphism and the efficacy of anti-hypertensive drug treatment on patient with essential hypertension[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(5): 538-544.

References

［1］Lim SS, Vos T, Flaxman AD, et al.A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010［J］. Lancet, 2012, 380(9859): 2224-2260.
［2］陈伟伟, 高润霖, 刘力生,等.《中国心血管病报告2014》概要［J］. 中国循环杂志, 2015,30(7):617-622.
［3］Bian K, Doursout MF, Murad F.Vascular system: role of nitric oxide in cardiovascular diseases［J］. J Clin Hypertens (Greenwich), 2008, 10(4): 304-310.
［4］Naseem KM. The role of nitric oxide in cardiovascular diseases［J］. Mol Aspects Med, 2005, 26(1-2): 33-65.
［5］Mungrue IN, Bredt DS, Stewart DJ, et al. From molecules to mammals: what's NOS got to do with it［J］? Acta Physiologica Scandinavica, 2003, 179(2): 123-135.
［6］Olson KR, Donald JA, Dombkowski RA, et al. Evolutionary and comparative aspects of nitric oxide, carbon monoxide and hydrogen sulfide［J］. Respir Physiol Neurobiol, 2012, 184(2): 117-129.
［7］Alderton WK, Cooper CE, Knowles RG.Nitric oxide synthases: structure, function and inhibition［J］. Biochem J, 2001, 357(Pt 3): 593-615.
［8］Kone BC, Kuncewicz T, Zhang W, et al. Protein interactions with nitric oxide synthases: controlling the right time, the right place, and the right amount of nitric oxide［J］. Am J Physiol Renal Physiol, 2003, 285(2): F178-190.
［9］Balligand JL, Feron O, Dessy C. eNOS activation by physical forces: from short-term regulation of contraction to chronic remodeling of cardiovascular tissues［J］. Physiol Rev, 2009, 89(2): 481-534.
［10］Huang PL, Huang Z, Mashimo H, et al. Hypertension in mice lacking the gene for endothelial nitric oxide synthase［J］. Nature, 1995, 377(6546): 239-242.
［11］Shesely EG, Maeda N, Kim HS, et al. Elevated blood pressures in mice lacking endothelial nitric oxide synthase［J］. Proc Natl Acad Sci U S A, 1996, 93(23): 13176-13181.
［12］Kubis N, Richer C, Domergue V, et al. Role of microvascular rarefaction in the increased arterial pressure in mice lacking for the endothelial nitric oxide synthase gene (eNOS-/-)［J］. J Hypertens, 2002, 20(8): 1581-1587.
［13］Wang L, Shen C, Yang S , et al. Association study of NOS3 gene polymorphisms and hypertension in the Han Chinese population［J］. Nitric Oxide, 2015, 51:1-6.
［14］张永莉. 高血压药物基因治疗研究进展［J］.中国老年心脑血管病杂志,2013,15(10)：1106-1108.
［15］郭道遐, 陈燕春, 王林红, 等. 高迁移率族蛋白1基因多态性与中国南方农村常用高血压药物疗效的关系［J］.中国临床药理学与治疗学,2014, 19(7):766-771.
［16］Kannel WB, Hjortland MC, McNamara PM, et al. Menopause and risk of cardiovascular disease: the Framingham study［J］. Ann Intern Med, 1976, 85(4): 447-452.
［17］Bostom AG, Cupples LA, Jenner JL, et al. Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study［J］. JAMA, 1996, 276(7): 544-548.
［18］Franklin SS, Gustin WT, Wong ND, et al. Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study［J］. Circulation, 1997, 96(1): 308-315.
［19］Safar ME. Pulse pressure, arterial stiffness, and cardiovascular risk［J］. Curr Opin Cardiol, 2000,15(4): 258-263.
［20］Shi G, Gu CC, Kraja AT, et al. Genetic effect on blood pressure is modulated by age the hypertension genetic epidemiology network study［J］. Hypertension, 2009, 53(1): 35-41.
［21］Tipton AJ, Sullivan JC. Sex differences in T cells in hypertension［J］. Clin Ther, 2014, 36(12): 1882-1900.
［22］Cheng S, Xanthakis V, Sullivan LM, et al. Blood pressure tracking over the adult life course patterns and correlates in the framingham heart study［J］. Hypertension, 2012, 60(6): 1393-1399.
［23］Ahmed SB, Fisher ND, Hollenberg NK. Gender and the renal nitric oxide synthase system in healthy humans［J］. Clin J Am Soc Nephrol, 2007, 2(5): 926-931.

[1]	CHEN Yan, ZHU Lijun, FANG Zhengmei, ZHU Hui, JIN Yuelong, SHEN Chong, YAO Yingshui. Association of insulin-like growth factor(IGF)-1 polymorphisms and efficacy of antihypertensive drugs [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(2): 171-179.
[2]	GUO Dao-xia, CHEN Yan-chun, WANG Lin-hong, LU Wei, SHEN Chong, YANG Song, ZHAO Xiang-hai, JIN Yue-long, YAO Ying-shui. Association of HMGB1 gene polymorphism and drug treatment in patient with essential hypertension [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(7): 766-771.
[3]	GUO Yu, ZHOU Hong-hao, LIU Zhao-qian. MiRNA and interindividual difference in drug response [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(4): 443-448.
[4]	YIN Fang, LI Yun-fei, HUANG Ji-han, LI Lu-jin, ZHENG Qing-shan. A example introduce: clinical design and quantitative evaluation of ambulatory blood pressure monitoring for once daily antihypertensive drugs [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(6): 666-671.
[5]	XU Cheng-hua, YANG Yu-wen, CAO Heng. Effectes of β₁-adrenergic receptor and CYP2D6 gene polymorphism on metoprolol antihypertension therapy [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(12): 1414-1418.
[6]	DING Zheng, DENG Jie, SONG Hong-tao. Advances in the influence of MDR1 gene polymorphisms on pharmacokinetics of related drugs [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(10): 1191-1196.
[7]	PENG Cui-ying, ZHOU Cui-lan, HE Qing-zhi. Association of TNF-α gene -308G/A polymorphism with essential hypertension in Han racial origin in Hunan [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(1): 57-60.
[8]	FAN Jian-feng, TANG Sheng-xing, WAN Jun, ZHU Wei-ping, LI Bi-long, ZHU Zheng-cai. Variations of pregnancy-associated plasma protein-A and C-reactive protein in essential hypertension patients with left ventricular hypertrophy [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(2): 203-206.
[9]	TANG Qiang, HUANG You-liang, YU Qun-jun, HUANG Qiong, YIN Ji-ye, ZHOUHong-hao, LIU Zhao-qian. Study on the relationship between the therapeutic effect of enalapril on blood pressure reduction and ACE genetic polymorphisms [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(1): 72-75.
[10]	ZHANG Wei, HE Yi-jing, ZHOU Hong-hao. Progress and research in pharmacogenetics of OATP1B1 [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(7): 721-729.
[11]	HUANG Hai-ying, ZHOU Hong-hao. GNB3 C825T and essential hypertension [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(3): 355-360.
[12]	CAO Dong-ping, LV Jun-e, LIU Yong-xin, YAO Wen-jing, RONG Chun-li, YU Wei. Comparison of valsartan/hydrochlorothiazide and valsartan in the treatment of hypertension [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2008, 13(10): 1177-1181.
[13]	HU Qun-li, LIANG Qun, CAI Qi-yun. Effect of circadian variability of dipper blood pressure induced by valsartan in patients with non-dipper essential hypertension on levels of aldosterone [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(1): 116-118.
[14]	JIANG De-chun, BAI Xiang-rong, WANG Yu-qin, LI Lin. Advances in studies on population pharmacokinetics of antiepileptic drugs and CYP450 gene polymorphisms [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(11): 1207-1212.
[15]	ZHANG Ping-yang, DENG You-bin, YANG Hao-yi, PAN Min, BI Xiao-jun. Ultrasonic study on effects of simvastatin on left ventricular mass in patients with essential hypertension [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(9): 1001-1004.