Sage Journals: Discover world-class research

Abstract

Introduction

Essential hypertension (EH) is a chronic condition characterized by elevated blood pressure without any identifiable cause. Being a complex disorder, EH involves both genetic and non-genetic factors. This study investigated the association of RAAS genes－AGT, ACE, and REN SNPs with EH in the North-Indian population of Jammu.

Methodology

A total of 805 participants (392-cases; 413-controls) were genotyped for seven SNPs. Logistical regression, t-test, and Chi-square statistics were used to calculate the significance levels.

Results

Out of the seven SNPs, AGT/rs1926722 and REN/rs2368564 showed a significant positive correlation with EH [OR = 1.58 (95% CI:1.02–2.45, adj. P = 0.03) and OR = 1.45 (95% CI:1.08–1.94, adj. P = 0.01), respectively]. The ACE/rs4295, on the contrary, showed a significant negative correlation with EH [OR = 0.67 (95% CI:0.49–0.90), adj. P = 0.008]. Interestingly, these correlations were found to be restricted to systolic pressure. The gene-gene interaction analysis revealed an additive interaction between AGT/rs1926722 and REN/rs2368564 and an antagonistic interaction between ACE/rs4295 and AGT/rs1926722 or REN/rs2368564.

Conclusion

The positive correlation of AGT/rs1926722 and REN/rs2368564 suggests an increased risk for EH, whereas the negative correlation of ACE/rs4295 with EH suggests a decreased risk for EH in the study population. To better understand the genetic causes of EH in the study population, it is necessary to screen more variants in the RAAS and other blood pressure-related genes.

Keywords

essential hypertension RAAS pathway case-control genetic association study systolic blood pressure diastolic blood pressure North India

Get full access to this article

View all access options for this article.

References

Iqbal

Jamal

. Essential hypertension. Treasure Island (FL): StatPearls, 2025.

Oparil

Acelajado

Bakris

, et al. Hypertension. Nat Rev Dis Primers 2018; 4: 18014.

Fuchs

Whelton

. High blood pressure and cardiovascular disease. Hypertension 2020; 75: 285–292.

Prevalence of raised blood pressure (SBP≥140 OR DBP≥90) [Available from: https://www.who.int/data/gho/indicator-metadata-registry/imr-details/2386.

Hypertension [Available from: https://www.who.int/news-room/fact-sheets/detail/hypertension.

Seenappa

Kulothungan

Mohan

, et al. District-wise heterogeneity in blood pressure measurements, prehypertension, raised blood pressure, and their determinants among Indians: national family health survey-5. Int J Public Health 2024; 69: 1606766.

O'Shaughnessy

. The genetics of essential hypertension. Br J Clin Pharmacol 2001; 51: 5–11.

Natekar

Olds

Lau

, et al. Elevated blood pressure: our family's fault? The genetics of essential hypertension. World J Cardiol 2014; 6: 327–337.

Curtis

. Genetic variants associated with hypertension risk: progress and implications. Pulse (Basel) 2024; 12: 19–26.

10.

Fountain

Kaur

Lappin

. Physiology, renin angiotensin system. Treasure Island (FL): StatPearls, 2025.

11.

Patel

Sanghavi

Morris

, et al. Angiotensin II. Treasure Island (FL): StatPearls, 2025.

12.

Amrani

Baba Hamed

Mesli Talebbendiab

. Association study between some renin-angiotensin system gene variants and essential hypertension in a sample of Algerian population: case control study. Ann Biol Clin (Paris) 2015; 73: 557–563.

13.

Birhan

Molla

Abdulkadir

, et al. Association of angiotensin-converting enzyme gene insertion/deletion polymorphisms with risk of hypertension among the Ethiopian population. PLoS One 2022; 17: e0276021.

14.

Bonney

Obirikorang

Quaye

, et al. Association between angiotensin-converting enzyme (ACE) insertion/deletion polymorphism and hypertension in a Ghanaian population. PLoS One 2024; 19: e0311692.

15.

Isordia-Salas

Santiago-German

Flores-Arizmendi

, et al. Polymorphisms in the renin-angiotensin system and eNOS Glu298Asp genes are associated with increased risk for essential hypertension in a Mexican population. J Renin Angiotensin Aldosterone Syst 2023; 2023: 4944238.

16.

Vazquez-Moreno

Locia-Morales

Peralta-Romero

, et al. AGT Rs4762 is associated with diastolic blood pressure in Mexicans with diabetic nephropathy. J Diabetes Complications 2021; 35: 107826.

17.

Zakirova

Abdullaeva

Mashkurova

, et al. Association of the single nucleotide polymorphisms in the renin-angiotensin-aldosterone system with hypertension in the Uzbek population. Turk Kardiyol Dern Ars 2024; 52: 182–188.

18.

Niu

Zhang

, et al. Synergistic effects of gene polymorphisms of the renin-angiotensin-aldosterone system on essential hypertension in Kazakhs in Xinjiang. Clin Exp Hypertens 2016; 38: 63–70.

19.

Ying

Wang

, et al. Association of the renin gene polymorphism, three angiotensinogen gene polymorphisms and the haplotypes with essential hypertension in the Mongolian population. Clin Exp Hypertens 2010; 32: 293–300.

20.

Sato

Katsuya

Nakagawa

, et al. Nine polymorphisms of angiotensinogen gene in the susceptibility to essential hypertension. Life Sci 2000; 68: 259–272.

21.

Wan

, et al. The alleles of AGT and HIF1A gene affect the risk of hypertension in plateau residents. Exp Biol Med (Maywood) 2022; 247: 237–245.

22.

Yang

, et al. Correlation between renin-angiotensin system gene polymorphisms and essential hypertension in the Chinese Yi ethnic group. J Renin Angiotensin Aldosterone Syst 2015; 16: 975–981.

23.

Simonyte

Kuciene

Medzioniene

, et al. Renin-angiotensin system gene polymorphisms and high blood pressure in Lithuanian children and adolescents. BMC Med Genet 2017; 18: 100.

24.

Padma

Charita

Swapna

, et al. Novel variants detected in AGT gene among patients with essential hypertension. J Renin Angiotensin Aldosterone Syst 2015; 16: 642–646.

25.

Krishnan

Sekar

Karunanithy

, et al. Association of angiotensin converting enzyme gene insertion/deletion polymorphism with essential hypertension in south Indian population. Genes Dis 2016; 3: 159–163.

26.

Hussain

Awan

Gujjar

, et al. A case control association study of ACE gene polymorphism (I/D) with hypertension in Punjabi population from Faisalabad, Pakistan. Clin Exp Hypertens 2018; 40: 186–191.

27.

Parchwani

Patel

Rawtani

, et al. Association of Mbo I-RFLP at the renin locus (rs2368564) with essential hypertension. Indian J Clin Biochem 2016; 31: 431–438.

28.

Sharma

Fokkens

Laubscher

, et al. No association between AGT gene polymorphisms with hypertension in a South African population. Diabetes Metab Syndr Obes 2024; 17: 1853–1865.

29.

Gunda

Nagalingam

Tirunilai

. Role of tagged SNPs of the AGT gene in causing susceptibility to essential hypertension. Clin Exp Hypertens 2016; 38: 520–525.

30.

Sun

Zhao

Miao

, et al. Polymorphisms of three genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system are not associated with blood pressure salt sensitivity: a systematic meta-analysis. Blood Press 2016; 25: 117–122.

31.

Mohana Vamsi

Swapna

Usha

, et al. Contribution of REN gene MBbo I polymorphism in conferring risk for essential hypertension: a case control study from South India. J Renin Angiotensin Aldosterone Syst 2013; 14: 242–247.

32.

Katsuya

Asai

, et al. Lack of correlation between Mbo I restriction fragment length polymorphism of renin gene and essential hypertension in Japanese. Hypertens Res 2001; 24: 295–298.

33.

Yuan

Tang

Chun

, et al. Angiotensinogen T174M and M235T variants and hypertension in the Hani and Yi minority groups of China. Biochem Genet 2009; 47: 344–350.

34.

Kahlon

Carlisle

Otero Mostacero

, et al. Angiotensinogen: more than its downstream products: evidence from population studies and novel therapeutics. JACC Heart Fail 2022; 10: 699–713.

35.

Corvol

Jeunemaitre

. Molecular genetics of human hypertension: role of angiotensinogen. Endocr Rev 1997; 18: 662–677.

36.

Shahid

Rehman

Akash

MSH

, et al. Genetic polymorphism in angiotensinogen and its association with cardiometabolic diseases. Metabolites 2022; 12.

37.

Zhu

Lin

Wang

, et al. The relationship among angiotensinogen genes polymorphisms and hs-CRP and coronary artery disease. J Clin Lab Anal 2019; 33: e22881.

38.

Adhikari

Sharma

Lhamu Sherpa

, et al. Impact of renin-angiotensin-aldosterone system (RAAS) gene polymorphism in essential hypertension and antihypertensive drug therapy: A review. Int J Hypertens 2025; 2025: 5530265.

39.

Apte

Tomar

Sharma

. Incidence of high altitude pulmonary edema in low-landers during re-exposure to high altitude after a sojourn in the plains. Med J Armed Forces India 2015; 71: 214–220.

40.

Peng

Zhang

, et al. The association between maternal and foetal REN gene polymorphisms and preeclampsia/eclampsia: a hybrid design study. Pregnancy Hypertens 2019; 18: 150–155.

41.

Elkina

Akimova

Shvarts

. Polymorphism of ACE, AGT, AGTR1 genes as genetic predictors of hypertension. Russ J Cardiol 2021.

42.

Zhang

, et al. Haplotype-based association of renin gene polymorphisms with essential hypertension in Han population of northern China. J Renin Angiotensin Aldosterone Syst 2017; 18: 1470320317744917.

43.

Sopori

Kavinay

Bhan

, et al. CLOCK Gene 3'UTR and exon 9 polymorphisms show a strong association with essential hypertension in a North Indian population. BMC Med Genomics 2024; 17: 289.

44.

Purkait

Halder

Thakur

, et al. Association of angiotensinogen gene SNPs and haplotypes with risk of hypertension in eastern Indian population. Clin Hypertens 2017.

45.

Shaw

Patel

Lala-Trindade

, et al. Pathophysiology of preeclampsia-induced vascular dysfunction and implications for subclinical myocardial damage and heart failure. JACC Adv 2024; 3: 100980.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.02 MB

0.01 MB

ACE,AGT,and REN nucleotide variants show significant correlation with essential hypertension in the North Indian population of Jammu and Kashmir

Abstract

Introduction

Methodology

Results

Conclusion

Keywords

Get full access to this article

References

Supplementary Material