Clinical Nephrology - Epidemiology - Clinical Trials

Kidney International (1997) 52, 473–477; doi:10.1038/ki.1997.355

Angiotensin-converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus and its relationship with diabetic nephropathy

Barrett W Jeffers1, Raymond O Estacio1, Mary V Raynolds1 and Robert W Schrier1

1Division of Renal Diseases and Hypertension, Division of General Internal Medicine, Denver Health and Hospitals, and Division of Cardiology, Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA

Correspondence: Dr Robert W Schrier, Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado Health Sciences Center, 4200 E. Ninth Ave., #B178, Denver, Colorado 80262, USA.

Received 27 September 1996; Revised 22 January 1997; Accepted 17 March 1997.

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Abstract

Angiotensin-converting enzyme gene polymorphism in non-insulin dependent diabetes mellitus and its relationship with diabetic nephropathy. Previous studies have shown that the angiotensin-converting enzyme (ACE) gene polymorphism is associated with an increased risk of vascular disease in non-diabetic patients. The present study was conducted on 509 NIDDM patients who underwent a screening test to determine their ACE genotype for the Appropriate Blood Pressure Control in Diabetes (ABCD) Trial. Various baseline indices were correlated with the three ACE polymorphisms. The genotype was determined through polymerase chain reaction amplification of the angiotensin-converting enzyme polymorphism. The univariate relationship between the presence of the DD genotype with nephropathy as measured by urinary albumin excretion (UAE), and a history coronary artery disease (CAD) was then examined. Finally, a multiple model for each UAE and CAD was created so as to determine the independent effects of the presence of the DD genotype on each diabetic complication. Univariately, the presence of the DD genotype was associated with diabetic nephropathy. Furthermore, in a multiple model predicting diabetic nephropathy, the presence of the DD genotype was independently associated with diabetic nephropathy (odds ratio = 2.8, 95% confidence interval 1.4 to 5.5) but not CAD. Thus, the ACE DD genotype in 509 non-Hispanic white NIDDM patients in a metropolitan area in the U.S. was independently associated with the presence of diabetic nephropathy and, therefore, may be potentially used as a marker for NIDDM patients at risk for developing diabetic nephropathy.

Keywords:

angiotensin converting enzyme, blood pressure and diabetes, diabetic nephropathy, genotype ACE DD and diabetes, NIDDM

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References

  1. National Diabetes Data Group: Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28:1039–1057, 1979
  2. Harris MI, Hadden WC, Knowler WC, Bennett PH: Prevalence and impaired glucose tolerance and plasma glucose levels in U.S. population aged 20–74 years. Diabetes 36:523–534, 1987 | Article | PubMed | ISI | ChemPort |
  3. Proceedings from the Conference on Measuring, Managing, and Improving Quality in the End-Stage Renal Disease Treatment Setting. Am J Kid Dis 24:228–388, 1994
  4. Marre M, Bernadet P, Gallois Y, Savagner F, Guyene TT, Hallab M, Cambien F, Passa P, Alhenc-Gelas F: Relationships between angiotensin I converting enzyme gene polymorphism, plasma levels, and diabetic retinal and renal complications. Diabetes 43:384–388, 1994 | Article | PubMed | ISI | ChemPort |
  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 86:1343–1346, 1990 | PubMed | ISI | ChemPort |
  6. Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F, Soubrier F: Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet 51:197–205, 1992 | PubMed | ISI | ChemPort |
  7. Costerousse O, Allegrini J, Lopez M, Alhenc-Gelas F: Angio tensin I-converting enzyme in human circulating mononuclear cells: Genetic polymorphism of expression in T lymphocytes. Biochem J 290:33–40, 1993 | PubMed | ISI | ChemPort |
  8. Cambien F, Costerousse O, Tiret L, Poirier O, Lecerf L, Gonzales MF, Evans A, Arveiler D, Cambou JP, Luc G, Rakotovao R, Ducimetiere P, Soubrier F, Alhenc-Gelas F: Plasma level and gene polymorphism of angiotensin-converting enzyme in relation to myocardial infarction. Circulation 90:669–676, 1994 | PubMed | ChemPort |
  9. Raynolds MV, Bristow MR, Bush EW, Abraham WT, Lowes BD, Zisman LS, Taft CS, Perryman MB: Angiotensin-converting enzyme DD genotype in patients with ischaemic dilated cardiomyopathy. Lancet 342:1073–1075, 1993 | Article | PubMed | ISI | ChemPort |
  10. Fujisawa T, Ikegami H, Shen GQ, Yamato E, Takekawa K, Nakagawa Y, Hamad AY, Ueda H, Rakugi H, Higaki J: Angiotensin I-converting enzyme gene polymorphism is associated with myocardial infarction, but not with retinopathy or nephropathy, in NIDDM. Diabetes Care 18:983–985, 1995 | Article | PubMed | ISI | ChemPort |
  11. Mizuiri S, Hemmi H, Inoue A, Yoshikawa H, Tanegashima M, Fushimi T, Ishigami M, Amagasaki Y, Ohara T, Shimatake H, Hasegawa A: Angiotensin-converting enzyme polymorphism and development of diabetic nephropathy in non-insulin dependent diabetes mellitus. Nephron 70:455–459, 1995 | PubMed | ISI | ChemPort |
  12. Schrier RW, Savage S: Appropriate blood pressure control in diabetes (ABCD) trial: Implications for complications. Am J Kid Dis 6:653–657, 1992
  13. Savage S, Johnson-Nagel N, Estacio RO, Feig PU, MacCarthy EP, Lokken NJ, Ziegler R, Schrier RW: The ABCD (appropriate blood pressure control in diabetes) trial: Rationale and design of a trial of hypertension control (moderate or intensive) in type II diabetes. Online J Clin Trials 2:1993
  14. WHO Study Group: Diabetes Mellitus—Technical Report Series 727. Geneva, World Health Organization, 1985
  15. Klenk DC: Determination of glycosolated hemoglobin by affinity chromotography: Comparison with calometric and ion exchange methods and effects of common interferences. Clin Chem 28:2088–2094, 1982 | PubMed | ChemPort |
  16. Fossati P, Drencipe L: Serum triglycerides determined calorimetrically with an enzyme that produces hydrogen peroxide. Clin Chem 28:2077–2080, 1982 | PubMed | ISI | ChemPort |
  17. Allain CC, Poon LS, Chan CS, Richmond V, Fu PC: Enzymatic determination of total serum cholesterol. Clin Chem 20:470–474, 1973
  18. Assman G, Schriewer H, Schmitz G, Hascle E: Quantification of high-density lipoprotein cholesterol by precipitation with phosphoungstic acid. MG CLE (abstract). Clin Chem 29:6, 1983
  19. Hilbourne LH, Lin PC, Higgins SA, Rodgerson DO: Evaluation of the Behring nephelometer for detection of low level urinary albumin. Am J Clin Pathol 93:405–410, 1990 | PubMed |
  20. Hofeldt FD: Diabetes and dyslipidemia disorders in the elderly, in Ethical Issues in the Care of the Elderly (3rd ed.) edited by JAHNIGEN D, SCHRIER RW, Boston, Blackwell Science, 1996
  21. Iwai N, Ohmichi N, Nakamura Y, Kinoshita M: DD genotype of the angiotensin-converting enzyme gene is a risk factor for left ventricular hypertrophy. Circulation 90:2622–2628, 1994 | PubMed | ISI | ChemPort |
  22. Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Bard JM, Bara L, Ricard S, Tiret L, Amouyel P, Alhenc-Gelas F, Soubrier F: Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 359:641–644, 1992 | Article | PubMed | ISI | ChemPort |
  23. Tiret L, Kee F, Poirier O, Nicaud V, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Amoyel P: Deletion polymorphism in angiotensin-converting enzyme gene associated with parental history of myocardial infarction. Lancet 341:991–992, 1993 | Article | PubMed | ISI | ChemPort |
  24. Ludwig EH, Cornell PS, Anderson JF, Marshall HW, Laloel JM, Ward RH: The ACE insertion/deletion polymorphism is inde pendently associated with myocardial infarction and body mass index but not with stenosis (abstract). Circulation 88(Suppl I):I–364, 1993
  25. Ruiz J, Blanche H, Cohen N, Velho G, Cambien F, Cohen D, Passa P, Froguel P: Insertion/deletion polymorphism of the angio tensin-converting enzyme gene is strongly associated with coronary heart disease in non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci USA 91:3662–3665, 1994 | Article | PubMed | ChemPort |
  26. Doria A, Warram JH, Krolewski AS: Genetic prediposition to diabetic nephropathy: Evidence for a role of the angiotensin I-converting enzyme gene. Diabetes 43:690–695, 1994 | Article | PubMed | ChemPort |
  27. Schmidt S, Schone N, Ritz E, Diabetic Nephropathy Study Group: Association of ACE gene polymorphism and diabetic ne phropathy? Kidney Int 47:1176–1181, 1995 | Article | PubMed | ISI | ChemPort |
  28. Klein R, Klein BE, Moss SE: Prevalence of gross microalbuminuria in older-onset diabetes. Diabetes Care 16:1325–1330, 1993 | Article | PubMed | ChemPort |
  29. Deckert T, Kofoed-Enevoldsen A, Norgaard K, Borch-Johnsen K, Feldt-RasmussenB, Jensen T: Microalbuminuria. Diabetes Care 15:1181–1191, 1992 | Article | PubMed | ISI | ChemPort |
  30. Gall MA, Rossing P, Skott P, Damsbo P, Vaag A, Bech K, Dejgaard A, Lauritzen M, Lauritzen E, Hougaard P: Prevalence of micro and macroalbuminuria, arterial hypertension, retinopathy and large vessel disease in European type 2 (non-insulin dependent) diabetic patients. Diabetologia 34:655–661, 1991 | Article | PubMed | ISI | ChemPort |
  31. Mauer M, Mogensen CE, Friedman EA: Diabetic nephropathy, in Diseases of the Kidney (6th ed) edited by SCHRIER RW, GOTTSHELF CW, Boston, Saunders, 1996
  32. Zmohrndrn VR, Christensen CK: Predicting diabetic nephropathy in insulin dependent patients. N Engl J Med 311:89–93, 1984 | PubMed | ISI | ChemPort |

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