Document Type : Research articles


1 Internal Medicine Department, Shahrekord University of Medical Sciences, Shahrekord, Iran

2 Department of Epidemiology and Biostatistics, School of Health, Shahrekord University of Medical Sciences, Shahrekord, Iran

3 Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

4 Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran

5 Cellular and Molecular research center, Shahrekord University of Medical Sciences, Shahrekord, Iran

6 Internal Medicine Department, Isfahan Medical School, Shahrekord, Iran


Background: Gene polymorphism of angiotensin-converting enzyme (ACE) may be associated with adverse prognosis and increased cardiovascular complications in hemodialysis patients.
Objectives: This study aimed to compare the frequency of ACE gene polymorphism in both hemodialysis patients and normal individuals considering echocardiographic findings.
Methods: This cross-sectional study included 110 hemodialysis patients (case) and 113 healthy subjects (control). Gene polymorphism of ACE was evaluated in both groups. ECG and echocardiography tests were performed for all patients. Correlations between gene polymorphisms and other variables were analyzed in this study. Polymerase chain reaction (PCR) was used to identify the short deletion allele (D with 190bp), large insertion allele (I with 490bp), and ID genotype which has both alleles.
Results: Case and control groups included 46 and 54 female and 64 and 59 male patients, respectively. There were no significant differences between the prevalence of DD, II, and DI alleles of the ACE gene with DI as the most common allele in both groups. No significant differences were found between systolic and diastolic blood pressure and heart rate in DD, DI, and II alleles of the case group. Echocardiographic findings of the patients showed no significant differences between DD, DI, and II genotypes of the case group and intraventricular septal end-diastole (IVSd), MVE vel, MVA vel, MVE/A ratio, MV DT, and MV Dec slope. The mean±SD left ventricular end-diastolic diameter (LVEDD) in II, ID, and DD patients were 4.3±0.72, 4.52±0.66, and 4.89±0.93 respectively (P=0.046).
Conclusion: The findings of the present study showed that there were no differences in the prevalence of alleles of an ACE gene in hemodialysis patients and control groups. Moreover, no significant associations were observed between alleles of an ACE gene in the patients' group and echocardiographic findings except in left ventricular end-diastolic diameter.

  1. Georgianos PI, Agarwal R. Resistant Hypertension in Chronic Kidney Disease (CKD): Prevalence, Treatment Particularities, and Research Agenda. Curr Hypertens Rep. 2020;22(10):1–8. doi: 10.1007/s11906-020-01081-x. [PMID: 32880742]
  2. Tomiyama C, Higa A, Dalboni MA, Cendoroglo M, Draibe SA, Cuppari L, et al. The impact of traditional and non-traditional risk factors on coronary calcification in pre-dialysis
    patients. Nephrol Dial Transplant. 2006;21(9):2464–71. doi: 10.1093/ndt/gfl291. [PMID:16735378].
  3. Patel UD, Young EW, Ojo AO, Hayward RA. CKD Progression and Mortality Among Older Patients With Diabetes. Am J Kidney Dis. 2005;46(3):406–14. doi: 10.1053/j.ajkd.2005.05.027. [PMID: 16129201].
  4. Ritz E, Orth SR. Nephropathy in Patients with Type 2 Diabetes Mellitus. N Engl J Med. 1999;341(15):1127–33. doi: 10.1056/NEJM199910073411506. [PMID: 10511612].
  5. Grundy SM, Benjamin IJ, Burke GL, Chait A, Eckel RH, Howard B V, et al. Diabetes and Cardiovascular Disease : A
    Statement for Healthcare Professionals From the American
    Heart Association. Circulation. 1999;100(10):1134–46.  doi: 10.1161/01.cir.100.10.1134. [PMID: 10477542].
  6. Shlipak MG, Fried LF, Cushman M, Manolio TA, Peterson D, Stehman-Breen C, et al. Cardiovascular Mortality Risk in Chronic Kidney Disease: comparison of traditional and
    novel risk factors . JAMA. 2005;293(14):1737-45. doi: 10.1001/jama.293.14.1737. [PMID: 15827312].
  7. Russo D, Palmiero G, De Blasio AP, Balletta MM, Andreucci VE. Coronary artery calcification in patients with CRF not undergoing dialysis. Am J Kidney Dis. 2004;44(6):1024–30.  doi: 10.1053/j.ajkd.2004.07.022. [PMID: 15558523].
  8. Nikodimopoulou M, Liakos S. Secondary hyperparathyroidism and target organs in chronic kidney disease. Hippokratia. 2011;15(1):33–8. [PMID: 21897756].
  9. Silverstein DM. Inflammation in chronic kidney disease: role in the progression of renal and cardiovascular disease. Pediatr Nephrol. 2009;24(8):1445–52. doi: 10.1007/s00467-008-1046-0.  [PMID: 19083024].
  10. Girndt M, Heine GH, Ulrich C, Köhler H, DialGene Consortium. Gene Polymorphism Association Studies in Dialysis: Vascular Access. Semin Dial. 2007;20(1):63–7. doi: 10.1111/j.1525-139X.2007.00243.x. [PMID: 17244124].
  11. Park HC, Choi SR, Kim BS, Lee TH, Kang BS, Choi KH, et al. Polymorphism of the ACE Gene in dialysis patients: overexpression of DD genotype in type 2 diabetic end-stage renal failure patients. Yonsei Med J. 2005;46(6):779–87. doi: 10.3349/ymj.2005.46.6.779. [PMID: 16385653].
  12. Rao M, Jaber BL, Balakrishnan VS, Consortium D. Genetics in Dialysis Series Editors: Bertrand L. Jaber and Vaidyanathapuram S. Balakrishnan: Gene Polymorphism Association Studies in Dialysis: Cardiovascular Disease. Semin Dial. 2005;18(3):217–25. doi: 10.1111/j.1525-139X.2005.18316.x. [PMID: 15934969].
  13. El-banawy H, Bedair R, Mohammed A. Angiotensin II type 1 receptor (A1166C) gene polymorphism in Egyptian adult hemodialysis patients. Alexandria J Med. 2015;51(4):339–45. doi: 10.1016/j.ajme.2014.12.003.
  14. Li XC , Zhu D, Zheng X, Zhang J, Zhuo JL.  Intratubular and intracellular renin-angiotensin system in the kidney: a
    unifying perspective in blood pressure control. Clin Sci (Lond). 2018 9;132(13):1383-1401. doi: 10.1042/CS20180121. [PMID:  29986878].
  15. Brewster UC, Perazella MA. The renin-angiotensin-aldosterone system and the kidney: effects on kidney disease. Am J Med. 2004;116(4):263–72. doi: 10.1016/j.amjmed.2003.09.034. [PMID:14969655].
  16. Yoshida H, Kuriyama S, Atsumi Y, Tomonari H, Mitarai T, Hamaguchi A, et al. Angiotensin I converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus. Kidney Int. 1996;50(2):657–64. doi: 10.1038/ki.1996.362. [PMID: 8840299].
  17. Borah PK, Shankarishan P, Hazarika NC, Mahanta J. Hypertension subtypes and angiotensin converting enzyme (ACE) gene polymorphism in Indian population. J Assoc Physicians India. 2012;60:11, 15–7. [PMID: 23409414].
  18. Tiago Veiga Pereira, Ane Cláudia Fernandes Nunes, Martina Rudnicki, Ricardo Magistroni, Alberto Albertazzi, Alexandre Costa Pereira, et al. Influence of CE I/D gene polymorphism in the progression of renal failure in autosomal dominant polycystic kidney disease: a meta-analysis. Nephrol Dial Transplant. 2006;21(11):3155-63.
  19. Samuelsson O, Attman P-O, Larsson R, Mulec H, Rymo L, Weiss L, et al. Angiotensin I-converting enzyme gene polymorphism in non-diabetic renal disease. Nephrol Dial Transplant. 2000;15(4):481–6. doi: 10.1093/ndt/15.4.481.
  20. Sarkar T, Singh NP, Kar P, Husain SA, Kapoor S, Pollipalli SK, et al. Does angiotensin-converting enzyme-1 (ACE-1) gene polymorphism lead to chronic kidney disease among hypertensive patients? .Ren Fail. 2016;38(5):765–9. doi: 10.3109/0886022X.2016.1160247. [PMID: 27050505].
  21. 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(4):1343–6.  doi: 10.1172/JCI114844. [PMID:1976655].
  22. Losito A, Kalidas K, Santoni S, Ceccarelli L, Jeffery S. Polymorphism of renin-angiotensin system genes in
    dialysis patients--association with cerebrovascular disease. Nephrol Dial Transplant. 2002;17(12):2184–8. doi: 10.1093/ndt/17.12.2184.
  23. Van Der Sman-De Beer F, Verhagen C, Rombach SM, Boorsma P, Van Manen JG, Korevaar JC, et al. ACE I/D polymorphism is associated with mortality in a cohort study of patients starting with dialysis. Kidney Int. 2005;68(5):2237–43. doi: 10.1111/j.1523-1755.2005.00681.x. [PMID: 16221224].
  24. Van DER SMAN-DE BEER F, Verhagen C, Rombach SM, Boorsma P, Van MANEN JG, Korevaar JC, et al. ACE I/D polymorphism is associated with mortality in a cohort study of patients starting with dialysis. Kidney Int. November 2005;68(5):2237–43.
  25. Vleming LJ, Van der Pijl JW, Lemkes HH, Westendorp RG, Maassen JA, Daha MR, et al. The DD genotype of the ACE gene polymorphism is associated with progression of diabetic nephropathy to end stage renal failure in IDDM. Clin Nephrol. 1999;51(3):133–40. [PMID: 10099885].
  26. Perna A, Ruggenenti P, Testa A, Spoto B, Benini R, Misefari V, et al. ACE genotype and ACE inhibitors induced renoprotection in chronic proteinuric nephropathies1. Kidney Int. 2000;57(1):
    274–81. doi: 10.1046/j.1523-1755.2000.00818.x. [PMID:10620209]
  27. Van Essen GG, Rensma PL, De Zeeuw D, Sluiter WJ, Scheffer H, Apperloo AJ, et al. Association between angiotensin-converting-enzyme gene polymorphism and failure of renoprotective therapy. Lancet .1996;347(8994):94–5. doi: 10.1016/s0140-6736(96)90213-5. [PMID: 8538349]
  28. Dijk MA., Breuning MH, Peters DJM, Chang PC. The ACE insertion/deletion polymorphism has no influence on progression of renal function loss in autosomal dominant polycystic kidney disease. Nephrol Dial Transplant. 2000;
    15(6):836–9.  doi: 10.1093/ndt/15.6.836. [PMID: 10831637].
  29. Albuquerque FN de, Brandão AA, Silva DA 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(1):70–9. doi: 10.5935/abc.20130229. [PMID: 24270863].
  30. Bahramali E, Rajabi M, Jamshidi J, Mousavi SM, Zarghami M, Manafi A, et al. Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a case-control study. BMJ Open. 2016;6(2):e010282. doi: 10.1136/bmjopen-2015-010282. [PMID: 26861937].
  31. Wang AY-M, Chan JC-N, Wang M, Poon E, Lui S-F, Li PK-T, et al. Cardiac hypertrophy and remodeling in relation to ACE and angiotensinogen genes genotypes in Chinese dialysis patients. Kidney Int. 2003;63(5):1899–907. doi: 10.1046/j.1523-1755.2003.00933.x. [PMID: 12675870].
  32. Osono E, Kurihara S, Hayama N, Sakurai Y, Ohwada K, Onoda N, et al. Insertion/deletion polymorphism in intron 16 of the ACE gene and left ventricular hypertrophy in patients with end-stage renal disease. Am J Kidney Dis. 1998;32(5):725–30. doi: 10.1016/s0272-6386(98)70126-x. [PMID: 9820440].
  33. Sakka Y, Babazono T, Sato A, Ujihara N, Iwamoto Y. ACE gene polymorphism, left ventricular geometry, and mortality in diabetic patients with end-stage renal disease. Diabetes Res Clin Pract. 2004;64(1):41–9. doi: 10.1016/j.diabres.2003.10.010. [PMID: 15036826]