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European Journal of Medical Research
Published in: European Journal of Medical Research 1/2015

Open Access 01-12-2015 | Research

Angiotensin-converting enzyme insertion/deletion polymorphism, 24-h blood pressure profile and left ventricular hypertrophy in hypertensive individuals: a cross-sectional study

Authors: Luciana Neves Cosenso-Martin, Renan Oliveira Vaz-de-Melo, Luana Rocco Pereira, Cláudia Bernardi Cesarino, Juan Carlos Yugar-Toledo, José Paulo Cipullo, Marcela Augusta de Souza Pinhel, Dorotéia Rossi Silva Souza, José Fernando Vilela-Martin

Published in: European Journal of Medical Research | Issue 1/2015

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Abstract

Background

The absence of nocturnal blood pressure dipping (ND) identified by 24-h ambulatory blood pressure monitoring (ABPM) correlates with a worse cardiovascular prognosis. The renin–angiotensin system influences blood pressure levels and the occurrence of target organ damage (TOD). Thus, the aim of this study was to correlate the angiotensin-converting enzyme gene (ACE) insertion/deletion (I/D) polymorphism with the 24-h blood pressure profile and TOD in hypertensive individuals.

Methods

155 non-diabetic hypertensive individuals on antihypertensive treatment underwent ABPM. Peripheral blood samples were drawn for biochemistry and genetic analysis of the ACE I/D polymorphism by polymerase chain reaction. ND was defined as ≥10 % differences in the mean systolic blood pressure (BP) during wakefulness and sleep.

Results

There were no differences in clinical or biochemical variables or TOD in respect to ND status, except for higher BP levels during sleep (p < 0.001) in non-dippers. There was significant difference in the prevalence of left ventricular hypertrophy (LVH) between ACE genotypes (II: 13.0 %; ID: 34.1 %; DD: 46.5 %; p value = 0.024) with an increased risk in carriers of the DD genotype (OR = 5.80; IC 95 % 1.50–22.44; p value = 0.011). Carriers of the D allele had higher systolic BP during wakefulness and by ABPM (p < 0.05), higher left ventricular mass (117.3 ± 50.0 vs. 100.3 ± 25.7; p value = 0.017) and higher prevalence of LVH (37.4 vs. 12.5 %; OR = 4.14; 95 % IC: 1.17–14.65; p value = 0.028), compared to the II genotype.

Conclusions

The DD genotype is associated with a higher prevalence of LVH. The presence of the D allele appears to be associated with higher mean 24-h and wake systolic BP measured by ABPM in hypertensive patients under antihypertensive treatment.
Literature
1.
Clement DL, De Buyzere ML, De Bacquer DA, de Leeuw PW, Duprez D, Fagard RH, et al. Office versus Ambulatory Pressure Study Investigators. Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension. N Eng J Med. 2003;348:2407–15.CrossRef
2.
Dolan E, Stanton A, Thijs L, Hinedi K, Atkins N, McClory S, et al. Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study. Hypertension. 2005;46:156–61.CrossRefPubMed
3.
Brotman DJ, Davidson MB, Boumitri M, Vidt DG. Impaired diurnal blood pressure variation and all-cause mortality. Am J Hypertens. 2008;21:92–7.CrossRefPubMed
4.
Vaz-de-Melo RO, Toledo JC, Loureiro AA, Cipullo JP, Moreno Júnior H, Martin JF. Absence of nocturnal dipping is associated with stroke and myocardium infarction. Arq Bras Cardiol. 2010;94:79–85.CrossRefPubMed
5.
Rigat B, Hubert C, Alhenc-Gelas F, Cambien F, Corvol P, Soubrier F. An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990;86:1343–6.PubMedCentralCrossRefPubMed
6.
Zintzaras E, Raman G, Kitsios G, Lau J. Angiotensin-converting enzyme insertion/deletion gene polymorphic variant as a marker of coronary artery disease: a meta-analysis. Arch Intern Med. 2008;168:1077–89.CrossRefPubMed
7.
Hamelin BA, Zakrzewski-Jakubiak M, Robitaille NM, Bogaty P, Labbé L, Turgeon J. Increased risk of myocardial infarction associated with angiotensin-converting enzyme gene polymorphism is age dependent. J Clin Pharmacol. 2011;51:1286–92.CrossRefPubMed
8.
Vaisi-Raygani A, Ghaneialvar H, Rahimi Z, Nomani H, Saidi M, Bahrehmand F, et al. The angiotensin-converting enzyme D allele is an independent risk factor for early onset coronary artery disease. Clin Biochem. 2010;43:1189–94.CrossRefPubMed
9.
Kato N, Tatara Y, Ohishi M, Takeya Y, Onishi M, Maekawa Y, et al. Angiotensin-converting enzyme single nucleotide polymorphism is a genetic risk factor for cardiovascular disease: a cohort study of hypertensive patients. Hypertens Res. 2011;34:728–34.CrossRefPubMed
10.
Perticone F, Ceravolo R, Cosco C, Trapasso M, Zingone A, Malatesta P, et al. Deletion polymorphism of angiotensin-converting enzyme gene and left ventricular hypertrophy in southern Italian patients. J Am Coll Cardiol. 1997;29:365–9.CrossRefPubMed
11.
Pontremoli R, Ravera M, Viazzi F, Nicolella C, Berruti V, Leoncini G, et al. Genetic polymorphism of the renin-angiotensin system and organ damage in essential hypertension. Kidney Int. 2000;57:561–9.CrossRefPubMed
12.
Fedor R, Asztalos L, Locsey L, Szabó L, Mányiné IS, Fagyas M, et al. Insertion/deletion polymorphism of the angiotensin-converting enzymes predicts left ventricular hypertrophy after renal transplantion. Transplant Proc. 2011;43:1259–60.CrossRefPubMed
13.
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 cardiovascular-renal risk. J Hypertens. 1997;15:1579–92.CrossRefPubMed
14.
Ng DP, Tai BC, Koh D, Tan KW, Chia KS. Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects. Diabetologia. 2005;48:1008–16.CrossRefPubMed
15.
Foffa I, Murzi M, Mariani M, Mazzone AM, Glauber M, Ait Ali L, Andreassi MG, et al. Angiotensin-converting enzyme insertion/deletion polymorphism is a risk factor for thoracic aortic aneurysm in patients with bicuspid or tricuspid aortic valves. J Thorac Cardiovasc Surg. 2012;144:390–5.CrossRefPubMed
16.
Chen Z, Xu F, Wei Y, Liu F, Qi H. Angiotensin converting enzyme insertion/deletion polymorphism and risk of pregnancy hypertensive disorders: a meta-analysis. J Renin Angiotensin Aldosterone Syst. 2012;13:184–95.CrossRefPubMed
17.
Reshetnikov EA, Akulova LY, Dobrodomova IS, Dvornyk VY, Polonikov AV, Churnosov MI. The insertion-deletion polymorphism of the ACE gene is associated with increased blood pressure in women at the end of pregnancy. J Renin Angiotensin Aldosterone Syst. 2013. doi:10.​1177/​1470320313501217​.PubMed
18.
Vilela-Martin JF, Vaz-de-Melo RO, Cosenso-Martin LN, Kuniyoshi CH, Yugar-Toledo JC, Pinhel MA, et al. Renin angiotensin system blockage associates with insertion/deletion polymorphism of angiotensin-converting enzyme in patients with hypertensive emergency. DNA Cell Biol. 2013;32:1–8.CrossRef
19.
Li Y, Yang P, Wu S, Yuan J, Shen C, Wu Y, et al. Gender-specific association between ACE gene I/D polymorphism and blood pressure response to hydrochlorothiazide in Han Chinese hypertensive patients. Biochem Genet. 2011;49:704–14.CrossRefPubMed
20.
Li X, Li Y, Jia N, Guo S, Chu S, Niu W. Angiotensin-converting enzyme gene deletion allele increases the risk of ventricular hypertrophy: evidence from a meta-analysis. Mol Biol Rep. 2012;39:10063–75.CrossRefPubMed
21.
Maeda Y, Ikeda U, Ebata H, Hojo Y, Seino Y, Nakagami H, et al. Angiotensin converting enzyme gene polymorphism in essential hypertension based on ambulatory blood pressure monitoring. Am J Hypertens. 1997;10:786–9.CrossRefPubMed
22.
O’Donnell CJ, Lindpaintner K, Larson MG, Rao VS, Ordovas JM, Schaefer EJ, et al. Evidence for association and genetic linkage of the angiotensin-converting enzyme locus with hypertension and blood pressure in men but not women in the Framingham Heart Study. Circulation. 1998;97:1766–72.CrossRefPubMed
23.
Matsubara M, Suzuki M, Fujiwara T, Kikuya M, Metoki H, Michimata M, et al. Angiotensin-converting enzyme I/D polymorphism and hypertension: the Ohasama study. J Hypertens. 2002;20:1121–6.CrossRefPubMed
24.
Staessen JA, Wang JG, Brand E, Barlassina C, Birkenhäger WH, Herrmann SM, et al. Effects of three candidate genes on prevalence and incidence of hypertension in a Caucasian population. J Hypertens. 2001;19:1349–58.CrossRefPubMed
25.
Todoroki M, Minami J, Ishimitsu T, Ohrui M, Matsuoka H. Relation between the angiotensin-converting enzyme insertion/deletion polymorphism and blood pressure in Japanese male subjects. J Hum Hypertens. 2003;17:713–8.CrossRefPubMed
26.
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.PubMedCentralCrossRefPubMed
27.
Freitas SR, Cabello PH, Moura-Neto RS, Dolinsky LC, Lima AB, Barros M, et al. Analysis of renin-angiotensin-aldosterone system gene polymorphisms in resistant hypertension. Braz J Med Biol Res. 2007;40:309–16.CrossRefPubMed
28.
Ramachandran V, Ismail P, Stanslas J, Shamsudin N, Moin S, Mohd Jas R. Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene with essential hypertension and type 2 diabetes mellitus in Malaysian subjects. J Renin Angiotensin Aldosterone Syst. 2008;9:208–14.CrossRefPubMed
29.
Bautista LE, Vargas CI, Oróstegui M, Gamarra G. Population-based case-control study of renin-angiotensin system genes polymorphisms and hypertension among Hispanics. Hypertens Res. 2008;31:401–8.CrossRefPubMed
30.
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;27:1384–91.CrossRefPubMed
31.
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 community-based study. J Hum Hypertens. 2009;23:176–81.CrossRefPubMed
32.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2004;27(Suppl. 1):S5–10.
33.
Atherosclerosis Department of Brazilian Society of Cardiology. Brazilian Guidelines for Dyslipidemia. Arq Bras Cardiol. 2004;88(Suppl 1):2–19.
34.
Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18:499–502.PubMed
35.
Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18:1440–63.CrossRefPubMed
36.
Ganau A, Devereux RB, Roman MJ, de Simone G, Pickering TG, Saba PS, et al. Patterns of left ventricular hypertrophy and geometric remodeling in essential hypertension. J Am Coll Cardiol. 1992;19:1550–8.CrossRefPubMed
37.
Mor-Avi V, Lang RM, Badano LP, Belohlavek M, Cardim NM, Derumeaux G, et al. Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography. Eur J Echocardiogr. 2011;12:167–205.CrossRefPubMed
38.
Information on V Brazilian Guidelines on Ambulatorial Blood Pressure Monitoring (ABPM V) e III Brazilian Guidelines on Home Blood Pressure Monitoring (HBPM III). Brazilian Society of Cardiology, Brazilian Society of Hypertension and Nephrology. 2011. http://​publicacoes.​cardiol.​br/​consenso/​2011/​diretriz_​mapa_​mrpa.​pdf Accessed 10 Dec 2014.
39.
Salazar LA, Hirata MH, Cavalli SA, Machado MO, Hirata RD. Optimized procedure for DNA isolation from fresh and cryopreserved clotted human blood useful in clinical molecular testing. Clin Chem. 1998;44(8 Pt1):1748–50.PubMed
40.
O’Dell SD, Humphries SE, Day IN. Rapid methods for population-scale analysis for gene polymorphisms: the ACE gene as an example. Br Heart J. 1995;73:368–71.PubMedCentralCrossRefPubMed
41.
Castellano M, Glorioso N, Cusi D, Sarzani R, Fabris B, Opocher G, et al. Genetic polymorphism of the renin-angiotensin-aldosterone system and arterial hypertension in the Italian population: the GENIPER Project. J Hypertens. 2003;21:1853–60.CrossRefPubMed
42.
Kotchen JM, McKean HE, Kotchen TA. Blood pressure trends with aging. Hypertension. 1982;4(5 Pt 2):III128–34.PubMed
43.
Kario K, Hoshide S, Umeda Y, Sato Y, Ikeda U, Nishiuma S, et al. Angiotensinogen and angiotensin-converting enzyme genotypes, and day and night blood pressures in elderly Japanese hypertensives. Hypertens Res. 1999;22:95–103.CrossRefPubMed
44.
Julve R, Chaves FJ, Rovira E, Pascual JM, Miralles A, Armengodd ME, et al. Polymorphism insertion/deletion of the ACE gene and ambulatory blood pressure circadian variability in essential hypertension. Blood Press Monit. 2001;6:27–32.CrossRefPubMed
45.
Higaki J, Baba S, Katsuya T, Sato N, Ishikawa K, Mannami T, et al. Deletion allele of angiotensin-converting enzyme gene increases risk of essential hypertension in Japanese men: the Suita Study. Circulation. 2000;101:2060–5.CrossRefPubMed
46.
Serdaroglu E, Mir S, Berdeli A. Hypertension and ace gene insertion/deletion polymorphism in pediatric renal transplant patients. Pediatr Transplant. 2005;9:612–7.CrossRefPubMed
47.
Deja G, Borowiec M, Fendler W, Pietrzak I, Szadkowska A, Machnica L, et al. Non-dipping and arterial hypertension depend on clinical factors rather than on genetic variability of ACE and RGS2 genes in patients with type 1 diabetes. Acta Diabetol. 2014;51:633–40.PubMedCentralCrossRefPubMed
48.
Jin Y, Kuznetsova T, Thijs L, Richart T, Stolarz-Skrzypek K, Liu Yanping, et al. Association of echocardiographic left ventricular structure with the ACE D/I polymorphism: a meta-analysis. J Renin Angiotensin Aldosterone Syst. 2011;12:243–53.CrossRef
49.
Gomez-Angelats E, de la Sierra A, Enjuto M, Sierra C, Oriola J, Francino A, et al. Lack of association between ACE gene polymorphism and left ventricular hypertrophy in essential hypertension. J Hum Hypertens. 2000;14:47–9.CrossRefPubMed
50.
Wu S, Hong J, Li H, Feng S, Qiao D, Gao M, et al. No correlation of polymorphism of angiotensin-converting enzyme genes with left ventricular hypertrophy in essential hypertension. Hypertens Res. 2000;23:261–4.CrossRefPubMed
51.
Hernández D, Lacalzada J, Salido E, Linares J, Barragán A, Lorenzo V, et al. Regression of left ventricular hypertrophy by lisinopril after renal transplantation: role of ACE gene polymorphism. Kidney Int. 2000;58:889–97.CrossRefPubMed
52.
Nakayama M, Nakano H, Tsuboi N, Kurosawa T, Tsuruta Y, Iwasaki Y, et al. The effect of angiotensin receptor blockade ARB on the regression of left ventricular hypertrophy in hemodialysis patients: comparison between patients with D allele and non-D allele ACE gene polymorphism. Clin Nephrol. 2005;64:358–63.CrossRefPubMed
53.
KüçüK MU, Sucu N, Firat SS, Aytaçoglu BN, Vezir Ö, Bozali C, et al. Role of ACE I/D gene polymorphisms on the effect of ramipril in inflammatory response and myocardial injury in patients undergoing coronary artery bypass grafts. Eur J Clin Pharmacol. 2014;70:1443–51.CrossRef
54.
Torun D, Sezer S, Arat Z, Pelit A, Yigit F, Ozdemir FN, et al. The frequency of combined target organ damage and the beneficial effect of ambulatory blood pressure monitoring in never treated mild-to-moderate hypertensive patients. Int Heart J. 2005;46:1073–82.CrossRefPubMed
55.
Albuquerque FN, Brandão AA, Silva DA, Mourilhe-Rocha R, Duque GS, Gondar AFP, et al. Angiotensin-converting enzyme genetic polymorphism: its impact on cardiac remodeling. Arq Bras Cardiol. 2014;102:70–9.PubMedCentralPubMed
56.
Huang W, Xie C, Zhou H, Yang T, Sun M. Association of the angiotensin-converting enzyme gene polymorphism with chronic heart failure in Chinese Han Patients. Eur J Heart Fail. 2004;6:23–7.CrossRefPubMed
Metadata
Title
Angiotensin-converting enzyme insertion/deletion polymorphism, 24-h blood pressure profile and left ventricular hypertrophy in hypertensive individuals: a cross-sectional study
Authors
Luciana Neves Cosenso-Martin
Renan Oliveira Vaz-de-Melo
Luana Rocco Pereira
Cláudia Bernardi Cesarino
Juan Carlos Yugar-Toledo
José Paulo Cipullo
Marcela Augusta de Souza Pinhel
Dorotéia Rossi Silva Souza
José Fernando Vilela-Martin
Publication date
01-12-2015
Publisher
BioMed Central
Published in
European Journal of Medical Research / Issue 1/2015
Electronic ISSN: 2047-783X
DOI
https://doi.org/10.1186/s40001-015-0166-9

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