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Renin-angiotensin gene polymorphism in children with uremia and essential hypertension

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Abstract.

The M235T polymorphism of the angiotensinogen (ANG) gene, the I/D polymorphism of the angiotensin converting enzyme (ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor (AT1R) gene were identified in 70 patients with end-stage renal disease [20 pediatric ESRD, aged 14.9±3.1, years blood pressure (BP) 139±14/91±13 mmHg, 50 adult ESRD , aged 48.7±18.7 years, BP 149.1±24/96.9±12 mmHg], 35 with juvenile essential hypertension (JEHT, aged 14.4±2.7 years, 24-h mean BP 135.37±7.37/72.4±7.68 mmHg), 130 adult healthy normotensive controls (aged 34.9±8.1 years, BP 117.8±8.7/78.7±8.5 mmHg), and 20 pediatric controls (aged 13.2±1.2 years, BP 109±6.5/71±5.9 mmHg). The ACE gene polymorphism was determined by polymerase chain reaction and the ANG and AT1R gene polymorphisms by single-step LightCycler technology. The ACE gene distribution of the Hungarian controls did not differ from the results of the other Caucasian populations. In JEHT and pediatric ESRD patients, the MT genotype of ANG was more frequent than in controls (JEHT 80%, pediatric ESRD 74% versus controls 50%, P<0.02). The DD genotype of ACE was over-represented in pediatric ESRD compared with controls (ESRD 45% versus controls 22%, P<0.05). There was a non-significant increase in the CC genotype frequency of AT1R in adult patients with ESRD compared with controls. In conclusion, there was an increased frequency of the ACE DD genotype in pediatric ESRD, which could be a genetic risk factor for the development of ESRD. Furthermore, there was a significant increase in MT genotype frequency of ANG M235T polymorphism in pediatric ESRD and JEHT. The role of AT1R gene polymorphism needs further investigation.

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References

  1. Pratt RE (1999) Angiotensin and control of cardiovascular structure. J Am Soc Nephrol 10:S120-S128

    CAS  PubMed  Google Scholar 

  2. Wolf G, Neilson EG (1999) Angiotensin II as a renal growth factor. J Am Soc Nephrol 3:1531–1540

    Google Scholar 

  3. Matsusaka T, Hymes J, Ichikawa I (1996) Angiotensin in progressive renal diseases: theory and practice. J Am Soc Nephr 7:2027–2043

    Google Scholar 

  4. Bloem LJ, Manatunga AK, Tewksbury DA, Pratt JH (1995) The serum angiotensinogen concentration and variants of the angiotensinogen gene in white and black children. J Clin Invest 95: 948–953

    Google Scholar 

  5. Winkelmann BR, Russ AP, Nauck M, Klein B, Bohm BO, Maier V, Zotz R, Matheis G, Wolf A, Wieland H, Gross W, Galton DJ, Marz W (1999) Angiotensinogen M235T polymorphism is associated with plasma angiotensinogen and cardiovascular disease. Am Heart J 137:698–705

    CAS  PubMed  Google Scholar 

  6. Rigat B, Hubert C, Alhene-Gelas F, Cambien F, Corvol P, Soubrier F (1990) An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 86:1343–1346

    CAS  PubMed  Google Scholar 

  7. Costerousse O, Allegrini J, Lopez M, Alhene-Gelas F (1993) Angiotensin I-converting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes. Biochem J 290:33–40

    CAS  PubMed  Google Scholar 

  8. Erdos E, Skidgel RA (1987) The angiotensin converting enzyme. Lab Invest 56:345–348

    CAS  PubMed  Google Scholar 

  9. Bonnardeaux A, Davies E, Jeunemaitre X, Féry I, Charru A, Clauser E, Tiret L, Cambien F, Corvol P, Soubrier F (1994) Angiotensin II type I receptor gene polymorphism in human essential hypertension. Hypertension 24:63–69

    CAS  PubMed  Google Scholar 

  10. Osterop AP, Kofflard MJ, Sandkuijl LA, Cate FJ ten, Krams R, Schalecamp MA, Danser AH (1998) AT1 receptor A/C 1166 polymorphism contributes to cardiac hypertrophy in subjects with hypertrophic cardiomyopathy. Hypertension 32:825–830

    CAS  PubMed  Google Scholar 

  11. Munroe PB, Caulfield MJ (2000) Genetics of hypertension. Curr Opin Genet Dev 10:325–329

    Article  CAS  PubMed  Google Scholar 

  12. Soergel M, Kirschstein M, Busch C, Danne T, Gellermann J, Holl R, Krull F, Reichert H, Reusz GS, Rascher W (1997) Oscillometric twenty-four-hour ambulatory blood pressure values in healthy children and adolescents: a multicenter trial including 1141 subjects. J Pediatr 130:178–184

    CAS  PubMed  Google Scholar 

  13. Woodhead JL, Fallon R, Figuerido H, Langdale J, Malcolm ABO (1987) Alternative methods of gene diagnosis. In: Davies KE (ed) Human genetic diseases. A practical approach. IRL Press, pp 56–57

  14. Chiu KC, McCarthy JE (1997) The insertion allele at the angiotensin I converting gene locus is associated with insulin resistance. Metabolism 46:395–399

    CAS  PubMed  Google Scholar 

  15. Malin R, Wirta V, Hiltunen TP, Lehtimaki T (2000) Rapid detection of angiotensinogen M/T235 polymorphism by fluorescence probe melting curves (letter). Clin Chem 46:880–881

    CAS  PubMed  Google Scholar 

  16. Taal MW (2000) Angiotensin-converting enzyme gene polymorphisms in renal disease: clinically relevant? Curr Opin Nephrol Hypertens 9: 651–657

    Article  CAS  PubMed  Google Scholar 

  17. Hohenfellner K, Hunley TE, Brezinska R, Brodhag P, Shyr Y, Brenner W, Habermehl P, Kon V (1999) ACE I/D gene polymorphism predicts renal damage in congenital uropathies. Pediatr Nephrol 13: 514–518

    CAS  PubMed  Google Scholar 

  18. El-Essawy AB, Berthoux P, Cécillon S, Depréle C, Thibaudin D, De Fillippis J-P. Alamartine E, Berthoux F (2002) Hypertension after renal transplantation and polymorphism of genes involved in essential hypertension: ACE, AGT, AT1R and ecNOS. Clin Nephrol 57:192–200

    CAS  PubMed  Google Scholar 

  19. Bengtsson K, Orho-Melander M, Lindblad U, Melander O, Bøg-Hansen E, Ranstam J, Rastam L, Groop L (1999) Polymorphism in the angiotensin converting enzyme but not in the angiotensinogen gene is associated with hypertension and type 2 diabetes: the Skaraborg Hypertension and diabetes project. J Hypertens 17:1569–1575

    CAS  PubMed  Google Scholar 

  20. Mizuiri S, Hemmi H, Kumanomidou H, Iwamoto M, Miyagi M, Sakai K, Aikawa A, Ohara T, Yamada K, Shimatake H, Hasegawa A (2001) Angiotensin-converting enzyme (ACE) I/D genotype and renal ACE gene expression. Kidney Int 60:1124–1130

    Article  CAS  PubMed  Google Scholar 

  21. Sagnella GA, Rothwell MJ, Onipinla AK, Wicks PD, Cook DG, Capuccio FP (1999) A population study of ethnic variations in the angiotensin-converting enzyme I/D polymorphism: relationships with gender, hypertension and impaired glucose metabolism. J Hypertens 17:657–664

    CAS  PubMed  Google Scholar 

  22. Freire MBS, Dijk DJ van , Erman A, Boner G, Warram JH, Krolewski AS (1998) DNA polymorphisms in the ACE gene, serum ACE activity and the risk of nephropathy in insulin-dependent diabetes mellitus. Nephrol Dial Transplant 13:2553–2558

    Article  CAS  PubMed  Google Scholar 

  23. Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel JM (1992) Molecular basis of human hypertension: role of angiotensinogen. Cell 71:169–180

    CAS  PubMed  Google Scholar 

  24. Jeunemaitre X, Charru A, Chatellier G, Dumont C, Sassano P, Soubrier F, Menard J, Corvol P (1993) M235T variant of the human angiotensinogen gene in unselected hypertensive patients. J Hypertens 11:S80–S81

    Google Scholar 

  25. Katsuya T, Koike G, Yee TW, Sharpe N, Jackson R, Norton R, Horiuchi M, Pratt RE, Dzau VJ, MacMahon S (1995) Association of angiotensinogen gene T235 variant with increased risk of coronary heart disease. Lancet 345:1600–1603

    CAS  PubMed  Google Scholar 

  26. Ishigami T, Umemura S, Iwamoto T, Tamura K, Hibi K, Yamaguchi S, Nyuui N, Kimura K, Miyazaki N, Ishii M (1995) Molecular variant of angiotensinogen gene is associated with coronary atherosclerosis. Circulation 91:951–954

    CAS  PubMed  Google Scholar 

  27. Gumprecht J, Zychma MJ, Grzeszczak W, Zukowska-Szczechowska E, End-Stage Renal Disease Study Group (2000) Angiotensin I-converting enzyme gene insertion/deletion and angiotensinogen M235 T polymorphisms: risk of chronic renal failure. Kidney Int 58:513–519

    Article  CAS  PubMed  Google Scholar 

  28. Hohenfellner K, Wingen AM, Nauroth O, Wühl E, Mehls O, Schaefer F (2001) Impact of ACE I/D gene polymorphism on congenital renal malformations. Pediatr Nephrol 16:356–361

    PubMed  Google Scholar 

  29. Samuelson O, Attman P-O, Larsson R, Mulec H, Rymo L, Weiss L, Ricksten A (2000) Angiotensin I-converting enzyme gene polymorphism in non-diabetic renal disease. Nephrol Dial Transpl 15:481–486

    Article  Google Scholar 

  30. Zee RYL, Lou YK, Lyn R, Morris BJ (1992) Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension. Biochem Biophys Res Commun 184:9–15

    CAS  PubMed  Google Scholar 

  31. Schunkert H, Hense HW, Holmer SR, Stender M, Perz S, Keil U, Lorell BH, Riegger GA (1994) Association between a deletion polymorphism of the angiotensin converting enzyme and left ventricular hypertrophy. N Eng J Med 330:1634–1638

    Article  CAS  Google Scholar 

  32. Iwai N, Ohmichi N, Nakamura Y, Kinoshita M (1994) DD genotype of the angiotensin-converting enzyme is a risk factor for left ventricular hypertrophy. Circulation 90:2622–2628

    CAS  PubMed  Google Scholar 

  33. Timmermans PB, Wong PC, Chiu AT, Herblin WF, Benfield P, Carini DJ, Lee RJ, Wexler RR, Saye JA, Smith RD (1993) Angiotensin II receptors and angiotension II receptor antagonists. Pharmacol Rev 45: 205–251

    CAS  PubMed  Google Scholar 

  34. Bonnardeaux A, Davies E, Jeunemaitre X, Fery I, Charru A, Clauser E, Tiret L, Cambien F, Corvol P, Soubrier F (1994) Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension 24:63–69

    CAS  PubMed  Google Scholar 

  35. Benetos A, Topouchian J, Ricard S, Gautier S, Bonnardeaux A, Asmar R, Poirier O, Soubrier F, Safar M, Cambien F (1995) Influence of angiotensin II type 1 receptor polymorphism on aortic stiffness in never treated hypertensive patients. Hypertension 26:44-47

    CAS  PubMed  Google Scholar 

  36. Wang WY, Zee RY, Morris BJ (1997) Association of angiotensin II type 1 receptor gene polymorphism with essential hypertension. Clin Genet 51:31–34

    CAS  PubMed  Google Scholar 

  37. Tiret L, Bonnardeaux A, Poirier O, Ricard S, Marques-Vidal P, Evans A, Arveiler D, Luc G, Kee F, Ducimetiere P, Soubrier F, Cambien F (1994) Synergistic effects of angiotensin-converting enzyme and angiotensin-II type 1 receptor gene polymorphism on risk of myocardial infarction. Lancet 344: 910–913

    CAS  PubMed  Google Scholar 

  38. Poirier O, Georges JL, Ricard S, Arveiler D, Ruidavets JB, Luc G, Evans A, Cambien F, Tiret L (1998) New polymorphisms of the angiotensin II type 1 receptor gene and their associations with myocardial infarction and blood pressure: the ECTIM study. Etude Cac-Témoin de l'Infarctus du Myocarde. J Hypertens 16:1443–1447

    CAS  PubMed  Google Scholar 

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Acknowledgements.

This study was supported by research grants OTKA 25010.T/10, FKFP 05886/2000, and ETT 673/1996. We are grateful to Ildikó Csipő and Csilla Horváth for their skillful technical assistance.

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Authors and Affiliations

  1. Department of Pediatrics, University of Szeged, Korányi fasor 14–15, 6720 Szeged, Hungary

    Ferenc Papp, Csaba Bereczki, Ibolya Haszon, Emőke Endreffy & Sándor Túri

  2. GAMBRO Dialysis Center, Szeged, Hungary

    Éva Kiss

  3. University of Wisconsin School of Medicine, Madison, Wisconsin, USA

    Aaron L. Friedman

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  1. Ferenc Papp
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  2. Aaron L. Friedman
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Correspondence to Sándor Túri.

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Papp, F., Friedman, A.L., Bereczki, C. et al. Renin-angiotensin gene polymorphism in children with uremia and essential hypertension. Pediatr Nephrol 18, 150–154 (2003). https://doi.org/10.1007/s00467-002-1032-x

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  • DOI: https://doi.org/10.1007/s00467-002-1032-x

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