AGTR1A1166C gene polymorphism is associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension: A retrospective analysis

Abstract

Objective: To investigate whether angiotensin II type 1 receptor (AGTR1 A1166C) gene polymorphism was associated with the effectiveness of valsartan monotherapy in Chinese patients with essential hypertension.

Methods: This retrospective analysis included 198 patients (⩾18 years of age) who received valsartan monotherapy (80 mg/day) for newly developed essential hypertension at the authors’ center between January 1, 2020 and December 31, 2023. Genotyping for AGTR1 A1166C gene polymorphism was done by polymerase chain reaction (PCR)-melting curve analysis of genomic DNA from peripheral blood samples. A dominant genetic model for AGTR1 A1166C (AA genotype versus AC + CC genotype) was used. Multivariate regression analysis of baseline variables and AGTR1 polymorphism was conducted to identify predictors of target blood pressure attainment (<140/90 mmHg) at the 4-week follow-up.

Results: The median age of the 198 patients was (53.7±13.5) years, and 58% were men. Genotyping assays showed that 164 patients had the AA genotype, and 34 patients were of the AC/CC genotype, including 30 with the AC genotype and 4 with the CC genotype. Allele distribution was consistent with Hardy Weinberg equilibrium. 109 Patients (55.1%) attained the blood pressure target. Multivariate analysis showed that smoking (versus no smoking, HR 0.314, 95% CI 0.159-0.619, P=0.001) and AGTR1 A1166C AA genotype (versus AC/CC, HR 2.927, 95% CI 1.296-6.611, P=0.023) were significant and independent predictors of target attainment. 25 Patients (73.5%) with AGTR1 A1166C AC/CC genotype attained the target versus 51.2% (51/164) of patients with AGTR1 A1166C AA genotype (P=0.017). Patients with AGTR1 A1166C AC/CC genotype had a significantly greater reduction in systolic blood pressure [(33.1±10.8) mmHg versus (29.2±11.7) mmHg in AA carriers; P=0.029)].

Conclusions: Hypertensive patients carrying one or two C alleles of the AGTR1 A1166C gene were more responsive to valsartan treatment.

Keywords

Essential hypertension / Angiotensin II type 1 receptor antagonist / Valsartan / Gene polymorphism

References

[1] Mills KT, Stefanescu A, He J. The global epidemiology of hypertension. Nat Rev Nephrol 2020; 16: 223-237.

[2] Gomez-Sanchez CE, Gomez-Sanchez EP. Aldosterone synthase inhibitors and the treatment of essential hypertension. J Clin Endocrinol Metab 2023; 108: e638-e639.

[3] NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: A pooled analysis of 1201 population-representative studies with 104 million participants. Lancet 2021; 398: 957-980.

[4] Lu Y, Lan T. Global, regional, and national burden of hypertensive heart disease during 1990-2019: An analysis of the global burden of disease study 2019. BMC Public Health 2022; 22: 841.

[5] Di Palo KE, Barone NJ. Hypertension and heart failure: Prevention, targets, and treatment. Cardiol Clin 2022; 40: 237-244.

[6] Muntner P, Hardy ST, Fine LJ, Jaeger BC, Wozniak G, Levitan EB, et al. Trends in blood pressure control among US adults with hypertension, 1999-2000 to 2017-2018. JAMA 2020; 324: 1190-1200.

[7] The Writing Committee of the Report on Cardiovascular Health and Diseases in China. Report on cardiovascular health and diseases in China 2021: An updated summary. J Geriatr Cardiol 2023; 20: 399-430.

[8] Lewington S, Lacey B, Clarke R, Guo Yu, Kong X, Yang L, et al. The burden of hypertension and associated risk for cardiovascular mortality in China. JAMA Intern Med 2016; 176: 524-532.

[9] Wang D, Wu H, Zhang Q, Zhou X, An Y, Zhao A, et al. Optimisation of warfarin-dosing algorithms for Han Chinese patients with CYP2C9*13 variants. Eur J Clin Pharmacol 2023; 79: 1315-1320.

[10] Gregory AT, Pepe S, Denniss AR, Kizana E, Chong JJH. Cell, gene and regenerative therapies in cardiovascular disease: Charting a course from the research bench to clinical utility. Heart Lung Circ 2023; 32: 765-768.

[11] Forrester SJ, Booz GW, Sigmund CD, Coffman TM, Kawai T, Rizzo V, et al. Angiotensin II signal transduction: An update on mechanisms of physiology and pathophysiology. Physiol Rev 2018; 98: 1627-1738.

[12] Murphy TJ, Alexander RW, Griendling KK, Runge MS, Bernstein KE. Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor. Nature 1991; 351: 233-236.

[13] Patel S, Hussain T. Synergism between angiotensin receptors ligands: Role of angiotensin-(1-7) in modulating AT2 R agonist response on nitric oxide in kidney cells. Pharmacol Res Perspect 2020; 8: e00667.

[14] Williams B, Mancia G, Spiering W, Rosei EA, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018; 39: 3021-3104.

[15] Special Writing Group of China Stroke Surveillance Report. China Stroke Surveillance Report 2021. Mil Med Res 2023; 10: 33.

[16] Siew-Keah L, Hann KW, Hoe SK, En LR, Chin LB, Chan MMS, et al. Awareness and perceived barriers in practicing healthy living to prevent hypertension among young adults in Malaysia. Asian Pac J Trop Med 2022; 15(12): 542-550.

[17] Riyadina W, Putri AS, Tuminah S, Suswanti I, Turana Y. Mental emotional disorder is a predictor of stroke incidence in adults: Ten year results of the Bogor Cohort Study on Non-Communicable Disease Risk Factors in Indonesia. Asian Pac J Trop Med 2024; 17(8): 351-357.

[18] Theodoridis X, Chourdakis M, Chrysoula L, Chroni V, Tirodimos I, Dipla K, et al. Adherence to the DASH diet and risk of hypertension: A systematic review and meta-analysis. Nutrients 2023; 15: 3261.

[19] Li LW, Cheng SS, Xu GQ. Identification of risk factors for hypertension in overweight and obese people and analysis of risk factor interactions: An R-based analysis. Front Cardiovasc Med 2023; 10: 1180698.

[20] Akpor OA, Olowolaju FO. Treatment satisfaction and medication adherence among hypertensive patients in a teaching hospital in Ekiti State, Nigeria. J Integr Nurs 2022; 4: 59-67.

[21] Parchwani DN, Patel DD, Rawtani J, Yadav D. Analysis of association of angiotensin II type 1 receptor gene A1166C gene polymorphism with essential hypertension. Indian J Clin Biochem 2018; 33: 53-60.

[22] Yu HZ, Li L, Dong B, Kong QQ, Niu W, Zhang K, et al. The impact of AGTR1 (A1166C) gene polymorphism on test indicators in hypertensive patients. Chin J Clin Lab Sci 2023; 41: 161-166.

[23] Chen K, Xiao P, Li G, Wang C, Yang C. Distributive characteristics of the CYP2C9 and AGTR1 genetic polymorphisms in Han Chinese hypertensive patients: A retrospective study. BMC Cardiovasc Disord 2021; 21: 73.

[24] de Denus S, Zakrzewski-Jakubiak M, Dubé MP, Bélanger F, Lepage S, Leblanc M, et al. Effects of AGTR1 A1166C gene polymorphism in patients with heart failure treated with candesartan. Ann Pharmacother 2008; 42: 925-932.

[25] Sun YX, Liao YH, Yuan Y, Feng L, Ma S, Wei F, et al. Influence of autoantibodies against AT1 receptor and AGTR1 polymorphisms on candesartan-based antihypertensive regimen: Results from the study of optimal treatment in hypertensive patients with anti-AT1-receptor autoantibodies trial. J Am Soc Hypertens 2014; 8: 21-27.

[26] Liu Y, Kong XM, Jiang YW, Zhao MM, Gao P, Cong X, et al. Association of AGTR1 A1166C and CYP2C9*3 gene polymorphisms with the antihypertensive effect of valsartan. Int J Hypertens 2022; 2022: 7677252.

[27] Masenga SK, Kabwe LS, Chakulya M, Kirabo A. Mechanisms of oxidative stress in metabolic syndrome. Int J Mol Sci 2023; 24: 7898.

[28] Dąbrowska E, Narkiewicz K. Hypertension and dyslipidemia: The two partners in endothelium-related crime. Curr Atheroscler Rep 2023; 25: 605-612.

[29] Khor YYY, Lee SK, Dharmani DM, Ling WC. Epigallocatechin-3-gallate exerts antihypertensive effects and improves endothelial function in spontaneously hypertensive rats. Asian Pac J Trop Biomed 2023; 13(7): 287-295.

[30] Nagarajan A, Doss VA. L-carvone attenuates myocardial injury and dyslipidemia in rats with isoproterenolinduced cardiac hypertrophy. Asian Pac J Trop Biomed 2023; 13(1): 17-25.