The Association of Angiotensin-converting Enzyme I/D and Angiotensinogen M235T Polymorphism Genes with Essential Hypertension: A Meta-analysis

Authors

  • Agus Wibowo Department of Biochemistry, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, National Institute of Health Research and Development, Indonesia Ministry of Health, Yogyakarta, Indonesia
  • Pramudji Hastuti Department of Biochemistry, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • Vinayanti Susanti Department of Internal Medicine Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia

DOI:

https://doi.org/10.3889/oamjms.2021.7628

Keywords:

Angiotensin-converting enzyme I/D, M235T, Polymorphism, Essential hypertension, Meta-analysis

Abstract

Objective:  Essential or primary hypertension in developing countries has become a major problem. Recent hypertension-related research has revealed susceptibility genes in genome-wide association studies. Several studies have associated angiotensin converting enzyme (ACE) I/D and angiotensinogen (AGT) M235T polymorphisms with essential hypertension, but results have been inconsistent. This meta-analysis aimed to clarify the association of AGT and ACE polymorphisms with the risk of primary hypertension.

Methods: PubMed, Embase database, Medline, Goggle Scholar, Scopus.com, as well portal Garuda (www.garuda.ristekdikti.go.id) and Cochrane were used to retrieve all publications from 2006-2020 relating risk factors for hypertension with ACE I/D and AGT M235T polymorphisms. The meta-analysis was conducted from January –April 2020. All association studies were identified and data extracted from each study. Revman 5.3 software was used for meta-analysis to estimate odds ratios (OR) after extracting data and evaluating the quality of the enrolled studies.

Results: A total of 27 studies (totaling 5,105 patients and 5196 controls) were identified. The overall effect suggested ACE I/D was significantly associated with primary hypertension (OR: 95%CI=1.51[1.29-1.77], p=0.004). There was no association between AGT M235T with risk of essential hypertension.

Conclusion: This meta-analysis found significant association between ACE I/D gene polymorphisms with primary hypertension susceptibility. However, the AGT M235T gene had no association with the risk of primary hypertension. The Adrenoreceptor-beta/Renin Angiotensin System (ADRB/RAS) A allele should be considered a risk factor for essential hypertension.  

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

References

Merlo J, Bengtsson-Boström K, Lindblad U, Råstam L, Melander O. Multilevel analysis of systolic blood pressure and ACE gene I/D polymorphism in 438 Swedish families a public health perspective. BMC Med Genet. 2006;7:14. https://doi.org/10.1186/1471-2350-7-14 PMid:16509973 DOI: https://doi.org/10.1186/1471-2350-7-14

Mondry A, Loh M, Liu P, Zhu AL, Nagel M. Polymorphisms of the insertion/deletion ACE and M235T AGT genes and hypertension: Surprising new findings and meta-analysis of data. BMC Nephrol. 2005;6:1-11. DOI: https://doi.org/10.1186/1471-2369-6-1

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. https://doi.org/10.1016/j.cca.2007.10.002 PMid:17977523 DOI: https://doi.org/10.1016/j.cca.2007.10.002

Gui-Yan W, Yan-Hua W, Qun X, Wei-Jun T, Ming-Ling G, Jian W, et al. Associations between RAS gene polymorphisms, environmental factors and hypertension in Mongolian people. Eur J Epidemiol. 2006;21(4):287-92. https://doi.org/10.1007/s10654-005-6006-4 PMid:16685579 DOI: https://doi.org/10.1007/s10654-005-6006-4

Crews DE, Williams SR. Molecular aspects of blood pressure. Hum Biol. 1999;71(4):475-503. PMid:10453099

Mohana VU, Swapna N, Surender RS, Vishnupriya S, Padma T. Gender-related association of AGT gene variants (M235T and T174M) with essential hypertension A case-control study. Clin Exp Hypertens. 2012;34(1):38-44. https://doi.org/10.3109/10641963.2011.618207 PMid:22148914 DOI: https://doi.org/10.3109/10641963.2011.618207

Das M, Pal S, Ghosh A. Angiotensin converting enzyme gene polymorphism (Insertion/Deletion) and hypertension in adult Asian Indians: A population-based study from Calcutta, India. Hum Biol. 2008;80(3):303-12. https://doi.org/10.3378/1534-6617-80.3.303 PMid:19130799 DOI: https://doi.org/10.3378/1534-6617-80.3.303

Bawazier LA, Sja’bani M, Haryana SM, Soesatyo MH, Sadewa AH. Relationship of angiotensin converting enzyme gene polymorphism and hypertension in Yogyakarta, Indonesia. Acta Med Indones. 2010;42(4):192-8. PMid:21063039

Saab YB, Gard PR, Overall ADJ. The association of hypertension with renin-angiotensin system gene polymorphisms in the Lebanese population. J Renin Angiotensin Aldosterone Syst. 2011;12(4):588-94. https://doi.org/10.1177/1470320311408465 PMid:21628354 DOI: https://doi.org/10.1177/1470320311408465

Kooffreh ME, Anumudu CI, Akpan EE, Ikpeme EV, Kumar PL. A study of the M235T variant of the angiotensinogen gene and hypertension in a sample population of Calabar and Uyo, Nigeria. Egypt J Med Hum Genet. 2013;14(1):13-9. http://doi.org/10.1016/j.ejmhg.2012.06.007 DOI: https://doi.org/10.1016/j.ejmhg.2012.06.007

Tripathi G, Dharmani P, Khan F, Sharma RK, Pandirikkal V, Agrawal S. High prevalence of ACE DD genotype among north Indian end stage renal disease patients. BMC Nephrol. 2006;7:1-7. https://doi.org/10.1186/1471-2369-7-15 PMid:17042963 DOI: https://doi.org/10.1186/1471-2369-7-15

Singh KD, Jajodia A, Kaur H, Kukreti R, Karthikeyan M. Gender specific association of RAS gene polymorphism with essential hypertension: A case-control study. Biomed Res Int. 2014;2014:538053. https://doi.org/10.1155/2014/538053 PMid:24860821 DOI: https://doi.org/10.1155/2014/538053

Heidari F, Vasudevan R, Mohd Ali SZ, Ismail P, Etemad A, Pishva SR, et al. Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene among Malay male hypertensive infjects in response to ACE inhibitors. J Renin Angiotensin Aldosterone Syst. 2015;16(4):872-9. https://doi.org/10.1177/1470320314538878 PMid:25002132 DOI: https://doi.org/10.1177/1470320314538878

Yang YL, Mo YP, He YS, Yang F, Xu Y, Li CC, 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(4):975-81. https://doi.org/10.1177/1470320315598697 PMid:26283679 DOI: https://doi.org/10.1177/1470320315598697

Alsafar H, Hassoun A, Almazrouei S, Kamal W, Almaini M, Odama U, et al. Association of angiotensin converting enzyme insertion-deletion polymorphism with hypertension in emiratis with Type 2 diabetes mellitus and its interaction with obesity status. Dis Markers. 2015;2015:536041. https://doi.org/10.1155/2015/536041 PMid:26491214 DOI: https://doi.org/10.1155/2015/536041

Tchelougou D, Kologo JK, Karou SD, Yaméogo VN, Bisseye C, Djigma FW, et al. Renin-angiotensin system genes polymorphisms and essential hypertension in Burkina Faso, West Africa. Int J Hypertens. 2015;2015:979631. https://doi.org/10.1155/2015/979631 PMid:26351579 DOI: https://doi.org/10.1155/2015/979631

Krishnan R, Sekar D, Karunanithy S, Subramanium S. Association of angiotensin converting enzyme gene insertion/deletion polymorphism with essential hypertension in south Indian population. Genes Dis. 2016;3(2):159-63. https://doi.org/10.1016/j.gendis.2016.03.001 PMid:30258884 DOI: https://doi.org/10.1016/j.gendis.2016.03.001

Ramu P, Umamaheswaran G, Shewade DG, Swaminathan RP, Dutta TK, Balachander J, et al. Candidate gene polymorphisms of renin angiotensin system and essential hypertension in a South Indian Tamilian population. Int J Hum Genet. 2011;11(1):31-40. https://doi.org/10.1080/09723757.2011.11886120 DOI: https://doi.org/10.1080/09723757.2011.11886120

Hussain M, Awan FR, Gujjar A, Hafeez S, Islam M. A case control association study of ACE gene polymorphism (I/D) with hypertension in Punjabi population from Faisalabad, Pakistan. Clin Exp Hypertens. 2018;40(2):186-91. https://doi.org/10.1080/10641963.2017.1356842 PMid:29058472 DOI: https://doi.org/10.1080/10641963.2017.1356842

Nawaz SK, Hasnain S. Effect of ACE polymorphisms on the association between noise and hypertension in a Pakistani population. J Renin Angiotensin Aldosterone Syst. 2011;12(4):516-20. https://doi.org/10.1177/1470320310395799 PMid:21436208 DOI: https://doi.org/10.1177/1470320310395799

Niu S, Zhang B, Zhang K, Zhu P, Li J, Sun Y, et al. Synergistic effects of gene polymorphisms of the renin-angiotensinaldosterone system on essential hypertension in Kazakhs in Xinjiang. Clin Exp Hypertens. 2016;38(1):63-70. https://doi.org/10.3109/10641963.2015.1060985 PMid:26305278 DOI: https://doi.org/10.3109/10641963.2015.1060985

Srivastava K, Sundriyal R, Meena PC, Bhatia J, Narang R, Saluja D. Association of angiotensin converting enzyme (insertion/deletion) gene polymorphism with essential hypertension in Northern Indian subjects. Genet Test Mol Biomarkers. 2012;16(3):174-7. https://doi.org/10.1089/gtmb.2011.0155 PMid:22103580 DOI: https://doi.org/10.1089/gtmb.2011.0155

Jiang X, Sheng H, Li J, Xun P, Cheng Y, Huang J, et al. Association between renin-angiotensin system gene polymorphism and essential hypertension: A communitybased study. J Hum Hypertens. 2009;23(3):176-81. https://doi.org/10.1038/jhh.2008.123 PMid:18830250 DOI: https://doi.org/10.1038/jhh.2008.123

AbdRaboh NR, Hemimi NS, Louka ML, El Bakrt S. Association of angiotensin converting enzyme insertion/deletion and angiotensin T235 polymorphism with risk of essential hypertension in Egyptian patients. Int J Cancer Res. 2012;8(3):69-82. https://doi.org/10.3923/ijcr.2012.69.82 DOI: https://doi.org/10.3923/ijcr.2012.69.82

Amrani A, Hamed MB, Talebbendiab FM. 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(5):557-63. https://doi.org/10.1684/abc.2015.1069 PMid:26489814 DOI: https://doi.org/10.1684/abc.2015.1069

Badaruddoza, Sudhir N. No evidence for association between ACE gene insertion (I)/deletion (D) polymorphism and hypertension in north Indian Punjabi population. Int J Hum Genet. 2012;12(3):177-83. https://doi.org/10.1080/09723757.2 012.11886180 DOI: https://doi.org/10.1080/09723757.2012.11886180

Mehri S, Mahjoub S, Hammami S, Zaroui A, Frih A, Betbout F, et al. Renin-angiotensin system polymorphisms about hypertension status and obesity in a Tunisian population. Mol Biol Rep. 2012;39(4):4059-65. https://doi.org/10.1007/s11033-011-1187-2 PMid:21779803 DOI: https://doi.org/10.1007/s11033-011-1187-2

Niu W, Qi Y, Cen W, Cui C, Zhuoma C. Genetic Polymorphisms of Angiotensinogen and. Hypertens Res. 2007;30(11):1129-37. https://doi.org/10.1291/hypres.30.1129 PMid:18250562 DOI: https://doi.org/10.1291/hypres.30.1129

Niu W, Qi Y, Hou S, Zhai X, Zhou W, Qiu C. Haplotype-based association of the renin-angiotensin-aldosterone system genes polymorphisms with essential hypertension among Han Chinese: The Fangshan study. J Hypertens. 2009;27(7):1384-91. https://doi.org/10.1097/HJH.0b013e32832b7e0d PMid:19412130 DOI: https://doi.org/10.1097/HJH.0b013e32832b7e0d

Rana G, Yadav S, Joshi S, Saraswathy KN. Association of DD genotype of angiotensin-converting enzyme gene (I/D) polymorphism with hypertension among a North Indian population. J Community Genet. 2018;9(1):51-5. https://doi.org/10.1007/s12687-017-0321-9 PMid:28770441 DOI: https://doi.org/10.1007/s12687-017-0321-9

Butler MG. Genetics of hypertension current status. J Med Liban. 2010;58(3):175-8. PMid:21462849

Tanira MO, Al Balushi KA. Genetic variations related to hypertension: A review. J Hum Hypertens. 2005;19(1):7-19. PMid:15361889 DOI: https://doi.org/10.1038/sj.jhh.1001780

Siyad AR. Hypertension. Hygeia J D Med. 2011;3(1):1-16.

Dickson ME, Sigmund CD. Genetic basis of hypertension: Revisiting angiotensinogen. Hypertension. 2006;48(1):14-20. https://doi.org/10.1161/01.HYP.0000227932.13687.60 PMid:16754793 DOI: https://doi.org/10.1161/01.HYP.0000227932.13687.60

Russo A, Di Gaetano C, Cugliari G, Matullo G. Advances in the genetics of hypertension: The effect of rare variants. Int J Mol Sci. 2018;19(3):688. https://doi.org/10.3390/ijms19030688 PMid:29495593 DOI: https://doi.org/10.3390/ijms19030688

Hopkins PN, Hunt SC. Genetics of hypertension. Genet Med. 2003;5(6):413-29. https://doi.org/10.1097/01.gim.0000096375.88710.a6 PMid:14614392 DOI: https://doi.org/10.1097/01.GIM.0000096375.88710.A6

Heidari F, Vasudevan R, Mohd Ali SZ, Ismail P, Arkani M. RAS genetic variants in interaction with ACE inhibitors drugs influences essential hypertension control. Arch Med Res. 2017;48(1):88-95. https://doi.org/10.1016/j.arcmed.2017.03.003 PMid:28577874 DOI: https://doi.org/10.1016/j.arcmed.2017.03.003

Ismail M, Akhtar N, Nasir M, Firasat S, Ayub Q, Khaliq S. Association between the angiotensin-converting enzyme gene insertion/deletion polymorphism and essential hypertension in young Pakistani patients. J Biochem Mol Biol. 2004;37(5):552-5. https://doi.org/10.5483/bmbrep.2004.37.5.552 PMid:15479618 DOI: https://doi.org/10.5483/BMBRep.2004.37.5.552

Naomi A, Fisher DL. Overview of the Renin-angiotensin System; 2019. p. 1-25. Available from: https://www.uptodate.com [Last accessed on 2021 Apr 20].

Seidel E, Scholl UI. Genetic mechanisms of human hypertension and their implications for blood pressure physiology. Physiol Genomics. 2017;49(11):630-52. https://doi.org/10.1152/physiolgenomics.00032.2017 DOI: https://doi.org/10.1152/physiolgenomics.00032.2017

Staessen JA, Wang JG, Ginocchio G, Petrov V, Saavedra AP, Soubrier F, et al. The deletion/insertion polymorphism of the angiotensin converting enzyme gene and cardiovascularrenal risk. J Hypertens. 1997;15(12 Pt 2):1579-92. https://doi.org/10.1097/00004872-199715120-00059 PMid:9488209 DOI: https://doi.org/10.1097/00004872-199715120-00059

Jeunemaitre X, Lifton RP, Charru A, Hunt SC, Hopkins PN, Williama RR, et al. Molecular basis of human hypertension: Role of angiotensinogen. Cell. 1992;71(1):169-80. https://doi.org/10.1016/0092-8674(92)90275-h PMid:1394429 DOI: https://doi.org/10.1016/0092-8674(92)90275-H

Staessen JA, Kuznetsova T, Wang JG, Emelianov D, Vlietinck R, Fagard R. M235T angiotensinogen gene polymorphism and cardiovascular renal risk. J Hypertens. 1999;17(1):9-17. https://doi.org/10.1097/00004872-199917010-00003 PMid:10100088 DOI: https://doi.org/10.1097/00004872-199917010-00003

Downloads

Published

2021-12-08

How to Cite

1.
Wibowo A, Hastuti P, Susanti V. The Association of Angiotensin-converting Enzyme I/D and Angiotensinogen M235T Polymorphism Genes with Essential Hypertension: A Meta-analysis. Open Access Maced J Med Sci [Internet]. 2021 Dec. 8 [cited 2024 Nov. 7];9(F):739-46. Available from: https://oamjms.eu/index.php/mjms/article/view/7628

Issue

Section

Meta-analytic Review Article

Categories