Papers

Effect of deletion polymorphism of angiotensin converting enzyme gene on progression of diabetic nephropathy during inhibition of angiotensin converting enzyme: observational follow up study

^a Steno Diabetes Centre, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark, ^b Institut National de la Sante et de la Recherche Medicale SC7, Paris

Correspondence to: Dr Parving.

Abstract

Objective: To evaluate the concept that an insertion/deletion polymorphism of the angiotensin converting enzyme gene predicts the therapeutic efficacy of inhibition of angiotensin converting enzyme on progression of diabetic nephropathy.
Design: Observational follow up study of patients with insulin dependent diabetes and nephropathy who had been treated with captopril for a median of 7 years (range 3-9 years).
Setting: Outpatient diabetic clinic in a tertiary referral centre.
Patients: 35 patients with insulin dependent diabetes and nephropathy were investigated during captopril treatment (median 75 mg/day (range 12.5 to 150 mg/day)) that was in many cases combined with a loop diuretic. 11 patients were homozygous for the deletion allele and 24 were heterozygous or homozygous for the insertion allele of the angiotensin converting enzyme gene.
Main outcome measures: Albuminuria, arterial blood pressure, and glomerular filtration rate according to insertion/deletion polymorphism.
Results: The two groups had comparable glomerular filtration rate, albuminuria, blood pressure, and haemoglobin A1c concentration at baseline. Captopril induced nearly the same reduction in mean blood pressure in the two groups--to 103 (SD 5) mm Hg in the group with the deletion and 102 (8) mm Hg in the group with the insertion--and in geometric mean albumin excretion--573 (antilog SE 1.3) µg/min and 470 (1.2) µg/min, respectively. The rate of decline in glomerular filtration rate (linear regression of all glomerular filtration rate measurements during antihypertensive treatment) was significantly steeper in the group homozygous for the double deletion allele than in the other group (mean 5.7 (3.7) ml/min/year and 2.6 (2.8) ml/min/year, respectively; P = 0.01). Multiple linear regression analysis showed that haemoglobin A1c concentration, albuminuria, and the double deletion genotype independently influenced the sustained rate of decline in glomerular filtration rate (R² (adjusted) = 0.51).
Conclusion: The deletion polymorphism in the angiotensin converting enzyme gene reduces the long term beneficial effect of angiotensin converting enzyme inhibition on the progression of diabetic nephropathy in patients with insulin dependent diabetes.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    StumbleUpon    Technorati    What's this?

Relevant Article

Effect of deletion polymorphism of angiotensin converting enzyme gene on progression of diabetic nephropathy

Michel Marre, Gilles Chatellier, and Francois Alhenc-Gelas
BMJ 1996 313: 1554-1555. [Extract] [Full Text]

This article has been cited by other articles:

• Hadjadj, S., Fumeron, F., Roussel, R., Saulnier, P.-J., Gallois, Y., Ankotche, A., Travert, F., Khalil, C. A., Miot, A., Alhenc-Gelas, F., Lievre, M., Marre, M., on behalf of the DIABHYCAR, DIAB2NEPHROGENE, and S, (2008). Prognostic Value of the Insertion/Deletion Polymorphism of the ACE Gene in Type 2 Diabetic Subjects: Results from the Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria or Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR), Diabete de type 2, Nephropathie et Genetique (DIAB2NEPHROGENE), and Survie, Diabete de type 2 et Genetique (SURDIAGENE) studies . Diabetes Care 31: 1847-1852 [Abstract] [Full text]  
• Ruggenenti, P., Bettinaglio, P., Pinares, F., Remuzzi, G. (2008). Angiotensin Converting Enzyme Insertion/Deletion Polymorphism and Renoprotection in Diabetic and Nondiabetic Nephropathies. CJASN 3: 1511-1525 [Abstract] [Full text]  
• Parving, H.-H., de Zeeuw, D., Cooper, M. E., Remuzzi, G., Liu, N., Lunceford, J., Shahinfar, S., Wong, P. H., Lyle, P. A., Rossing, P., Brenner, B. M. (2008). ACE Gene Polymorphism and Losartan Treatment in Type 2 Diabetic Patients With Nephropathy. J. Am. Soc. Nephrol. 19: 771-779 [Abstract] [Full text]  
• Arfa, I., Abid, A., Nouira, S., Elloumi-Zghal, H., Malouche, D., Mannai, I., Zorgati, M. M., Ben Alaya, N., Rebai, A., Zouari, B., Ben Ammar, S., Ben Rayana, M. C., Hmida, S., Blousa-Chabchoub, S., Abdelhak, S. (2008). Lack of association between the angiotensin-converting enzyme gene (I/D) polymorphism and diabetic nephropathy in Tunisian type 2 diabetic patients. Journal of Renin-Angiotensin-Aldosterone System 9: 32-36 [Abstract]  
• Yates, R. B., Stafford-Smith, M. (2006). The genetic determinants of renal impairment following cardiac surgery.. SEMIN CARDIOTHORAC VASC ANESTH 10: 314-326 [Abstract]  
• Weekers, L., Bouhanick, B., Hadjadj, S., Gallois, Y., Roussel, R., Pean, F., Ankotche, A., Chatellier, G., Alhenc-Gelas, F., Lefebvre, P. J., Marre, M. (2005). Modulation of the Renal Response to ACE Inhibition by ACE Insertion/Deletion Polymorphism During Hyperglycemia in Normotensive, Normoalbuminuric Type 1 Diabetic Patients. Diabetes 54: 2961-2967 [Abstract] [Full text]  
• Jacobsen, P. K. (2005). Review: Preventing End-Stage Renal Disease in Diabetic Patients -- Dual Blockade of the Renin-Angiotensin System (Part II). Journal of Renin-Angiotensin-Aldosterone System 6: 55-68 [Abstract]  
• Jacobsen, P. K. (2005). Preventing end stage renal disease in diabetic patients -- genetic aspect (part I). Journal of Renin-Angiotensin-Aldosterone System 6: 1-14 [Abstract]  
• Narita, I, Goto, S, Saito, N, Song, J, Omori, K, Kondo, D, Sakatsume, M, Gejyo, F (2003). Renoprotective efficacy of renin-angiotensin inhibitors in IgA nephropathy is influenced by ACE A2350G polymorphism. J. Med. Genet. 40: e130-130 [Full text]  
• Jacobsen, P., Tarnow, L., Carstensen, B., Hovind, P., Poirier, O., Parving, H.-H. (2003). Genetic Variation in the Renin-Angiotensin System and Progression of Diabetic Nephropathy. J. Am. Soc. Nephrol. 14: 2843-2850 [Abstract] [Full text]  
• Andersen, S., Jacobsen, P., Parving, H.-H. (2003). ACE Insertion/Deletion Genotypes and Angiotensin II Receptor Blockade in Diabetic Nephropathy: Is there a light at the end of the tunnel?. Diabetes Care 26: 2962-2963 [Full text]  
• Susztak, K., Sharma, K., Schiffer, M., McCue, P., Ciccone, E., Bottinger, E. P. (2003). Genomic Strategies for Diabetic Nephropathy. J. Am. Soc. Nephrol. 14: S271-278 [Abstract] [Full text]  
• Takahashi, N., Hagaman, J. R., Kim, H.-S., Smithies, O. (2003). Minireview: Computer Simulations of Blood Pressure Regulation by the Renin-Angiotensin System. Endocrinology 144: 2184-2190 [Abstract] [Full text]  
• Andersen, S., Tarnow, L., Cambien, F., Rossing, P., Juhl, T. R., Deinum, J., Parving, H.-H. (2003). Long-Term Renoprotective Effects of Losartan in Diabetic Nephropathy: Interaction with ACE insertion/deletion genotype?. Diabetes Care 26: 1501-1506 [Abstract] [Full text]  
• Mogensen, C. E. (2003). Genetics and Diabetic Renal Disease: Still a big black hole. Diabetes Care 26: 1631-1632 [Full text]  
• van der Kleij, F. G. H., de Jong, P. E., Henning, R. H., de Zeeuw, D., Navis, G. (2002). Enhanced Responses of Blood Pressure, Renal Function, and Aldosterone to Angiotensin I in the DD Genotype Are Blunted by Low Sodium Intake. J. Am. Soc. Nephrol. 13: 1025-1033 [Abstract] [Full text]  
• Caramori, M. L., Kim, Y., Huang, C., Fish, A. J., Rich, S. S., Miller, M. E., Russell, G., Mauer, M. (2002). Cellular Basis of Diabetic Nephropathy: 1. Study Design and Renal Structural-Functional Relationships in Patients With Long-Standing Type 1 Diabetes. Diabetes 51: 506-513 [Abstract] [Full text]  
• Joss, N., Paterson, K.R., Deighan, C.J., Simpson, K., Boulton-Jones, J.M. (2002). Diabetic nephropathy: how effective is treatment in clinical practice?. QJM 95: 41-49 [Abstract] [Full text]  
• Solini, A., Dalla Vestra, M., Saller, A., Nosadini, R., Crepaldi, G., Fioretto, P. (2002). The Angiotensin-Converting Enzyme DD Genotype Is Associated With Glomerulopathy Lesions in Type 2 Diabetes. Diabetes 51: 251-255 [Abstract] [Full text]  
• Elung-Jensen, T., Heisterberg, J., Kamper, A.-L., Sonne, J., Strandgaard, S., Larsen, N. E. (2001). High serum enalaprilat in chronic renal failure. Journal of Renin-Angiotensin-Aldosterone System 2: 240-245 [Abstract]  
• Fava, S., Azzopardi, J., Ellard, S., Hattersley, A. T. (2001). ACE Gene Polymorphism as a Prognostic Indicator in Patients With Type 2 Diabetes and Established Renal Disease. Diabetes Care 24: 2115-2120 [Abstract] [Full text]  
• Huang, W., Gallois, Y., Bouby, N., Bruneval, P., Heudes, D., Belair, M.-F., Krege, J. H., Meneton, P., Marre, M., Smithies, O., Alhenc-Gelas, F. (2001). Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse. Proc. Natl. Acad. Sci. USA 10.1073/pnas.231476798v1 [Abstract] [Full text]  
• HADJADJ, S., BELLOUM, R., BOUHANICK, B., GALLOIS, Y., GUILLOTEAU, G., CHATELLIER, G., ALHENC-GELAS, F., MARRE, M. (2001). Prognostic Value of Angiotensin-I Converting Enzyme I/D Polymorphism for Nephropathy in Type 1 Diabetes Mellitus: A Prospective Study. J. Am. Soc. Nephrol. 12: 541-549 [Abstract] [Full text]  
• Kvetny, J., Gregersen, G., Pedersen, R. S. (2001). Randomized placebo-controlled trial of perindopril in normotensive, normoalbuminuric patients with type 1 diabetes mellitus. QJM 94: 89-94 [Abstract] [Full text]  
• Mogensen, C. E., Neldam, S., Tikkanen, I., Oren, S., Viskoper, R., Watts, R. W, Cooper, M. E (2000). Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ 321: 1440-1444 [Abstract] [Full text]  
• Ha, S.-K., Yong Lee, S., Su Park, H., Ho Shin, J., Jung Kim, S., Hun Kim, D., Rae Kim, K., Yung Lee, H., Suk Han, D. (2000). ACE DD genotype is more susceptible than ACE II and ID genotypes to the antiproteinuric effect of ACE inhibitors in patients with proteinuric non-insulin-dependent diabetes mellitus. Nephrol Dial Transplant 15: 1617-1623 [Abstract] [Full text]  
• Crisan, D., Carr, J. (2000). Angiotensin I-Converting Enzyme: Genotype and Disease Associations. J. Mol. Diagn. 2: 105-115 [Full text]  
• Samuelsson, 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 Transplant 15: 481-486 [Abstract] [Full text]  
• Parving, H.-H. (2000). Blockade of the renin-angiotensin-aldosterone system and renal protection in diabetes mellitus. Journal of Renin-Angiotensin-Aldosterone System 1: 30-31  
• Redon, J., Chaves, F. J., Liao, Y., Pascual, J. M., Rovira, E., Armengod, M. E., Cooper, R. S. (2000). Influence of the I/D Polymorphism of the Angiotensin-Converting Enzyme Gene on the Outcome of Microalbuminuria in Essential Hypertension. Hypertension 35: 490-495 [Abstract] [Full text]  
• Okamura, A., Ohishi, M., Rakugi, H., Katsuya, T., Yanagitani, Y., Takiuchi, S., Taniyama, Y., Moriguchi, K., Ito, H., Higashino, Y., Fujii, K., Higaki, J., Ogihara, T., Higaki, J. (1999). Pharmacogenetic Analysis of the Effect of Angiotensin-Converting Enzyme Inhibitor on Restenosis After Percutaneous Transluminal Coronary Angioplasty. ANGIOLOGY 50: 811-822 [Abstract]  
• MAIER, L. A., RAYNOLDS, M. V., YOUNG, D. A., BARKER, E. A., NEWMAN, L. S. (1999). Angiotensin-1 Converting Enzyme Polymorphisms in Chronic Beryllium Disease. Am. J. Respir. Crit. Care Med. 159: 1342-1350 [Abstract] [Full text]  
• Brown, N. J., Vaughan, D. E. (1998). Angiotensin-Converting Enzyme Inhibitors. Circulation 97: 1411-1420 [Abstract] [Full text]  
• Yudkin, J. S., Andres, C., Mohamed-Ali, V., Gould, M., Panahloo, A., Haines, A. P., Humphries, S., Talmud, P. (1997). The Angiotensin-Converting Enzyme Gene and the Angiotensin II Type I Receptor Gene as Candidate Genes for Microalbuminuria : A Study in Nondiabetic and Non–Insulin-Dependent Diabetic Subjects. Arterioscler. Thromb. Vasc. Bio. 17: 2188-2191 [Abstract] [Full text]  
• Marre, M., Chatellier, G., Alhenc-Gelas, F. (1996). Effect of deletion polymorphism of angiotensin converting enzyme gene on progression of diabetic nephropathy. BMJ 313: 1554c-1555 [Full text]  
• (1996). DIABETES AND THE GENETICS OF RENAL FAILURE. JWatch General 1996: 7-7 [Full text]  
• Huang, W., Gallois, Y., Bouby, N., Bruneval, P., Heudes, D., Belair, M.-F., Krege, J. H., Meneton, P., Marre, M., Smithies, O., Alhenc-Gelas, F. (2001). Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse. Proc. Natl. Acad. Sci. USA 98: 13330-13334 [Abstract] [Full text]