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 (original) (raw)
Pathophysiology / Complications| September 01 2008
1Centre Hospitalier Universitaire Poitiers, Endocrinology, Diabetology, Poitiers, France
2Institut National de la Santé et de la Recherche Médicale, U927, Poitiers, France
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3Institut National de la Santé et de la Recherche Médicale, U695, Paris, France
4Unité de Formation et de Recherche Médecine Xavier Bichat, Université Paris 7 Diderot, Paris, France
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3Institut National de la Santé et de la Recherche Médicale, U695, Paris, France
4Unité de Formation et de Recherche Médecine Xavier Bichat, Université Paris 7 Diderot, Paris, France
5Endocrinologie-Diabetologie-Nutrition, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France
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6Centre Hospitalier Universitaire Poitiers, France and Institut National de la Santé et de la Recherche Médicale, CIC 0802, Poitiers, France
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Yves Gallois, PHARMD, PHD
7Biochemistry, Centre Hospitalier Universitaire, Angers, France
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5Endocrinologie-Diabetologie-Nutrition, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France
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3Institut National de la Santé et de la Recherche Médicale, U695, Paris, France
4Unité de Formation et de Recherche Médecine Xavier Bichat, Université Paris 7 Diderot, Paris, France
5Endocrinologie-Diabetologie-Nutrition, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France
8CIC Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France
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3Institut National de la Santé et de la Recherche Médicale, U695, Paris, France
4Unité de Formation et de Recherche Médecine Xavier Bichat, Université Paris 7 Diderot, Paris, France
5Endocrinologie-Diabetologie-Nutrition, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France
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1Centre Hospitalier Universitaire Poitiers, Endocrinology, Diabetology, Poitiers, France
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François Alhenc-Gelas, MD, PHD;
François Alhenc-Gelas, MD, PHD
9Institut National de la Santé et de la Recherche Médicale, U652, Paris, France
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10Faculté de Médecine Laënnec, Université Claude Bernard Lyon 1, Lyon, France
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3Institut National de la Santé et de la Recherche Médicale, U695, Paris, France
4Unité de Formation et de Recherche Médecine Xavier Bichat, Université Paris 7 Diderot, Paris, France
5Endocrinologie-Diabetologie-Nutrition, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France
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Diabetes Care 2008;31(9):1847–1852
Citation
Samy Hadjadj, Frédéric Fumeron, Ronan Roussel, Pierre-Jean Saulnier, Yves Gallois, Amos Ankotche, Florence Travert, Charbel Abi Khalil, Aurélie Miot, François Alhenc-Gelas, Michel Lievre, Michel Marre, on behalf of the DIABHYCAR, DIAB2NEPHROGENE, and SURDIAGENE study groups; 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 1 September 2008; 31 (9): 1847–1852. https://doi.org/10.2337/dc07-2079
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OBJECTIVE—We tested whether determination of the ACE insertion/deletion polymorphism is useful for renal and cardiovascular prognoses of type 2 diabetic subjects.
RESEARCH DESIGN AND METHODS—The French participants (3,126 of 4,912) in the Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria or Proteinuria, Cardiovascular Events, and Ramipril (DIABHYCAR) trial were studied for their prognosis over 4 years according to their ACE insertion/deletion polymorphism. We used two cohorts of French type 2 diabetic patients for replication: a 3-year follow-up study (n = 917; Survie, Diabete de type 2 et Genetique [SURDIAGENE] study) and a case-control study on diabetic nephropathy (n = 1,277; Diabete de type 2, Nephropathie et Genetique [DIAB2NEPHROGENE] study). We investigated the effect of the insertion/deletion polymorphism on the primary outcome in the DIABHYCAR trial (defined as the first of the following events to occur: cardiovascular death, nonfatal myocardial infarction, stroke, heart failure leading to hospital admission, or end-stage renal failure) and its components.
RESULTS—In DIABHYCAR, the primary outcome and most of its components were not affected by the ACE insertion/deletion genotype. Only renal outcome was favored by the I allele (P = 0.03). The risk of myocardial infarction was not affected by ACE genotype, but the probability of fatal outcome increased with the number of D alleles (P < 0.03). In SURDIAGENE, the association between the ACE I allele and renal outcome was not replicated. In DIAB2NEPHROGENE, no association was found with nephropathy.
CONCLUSIONS—We were not able to demonstrate the manifest usefulness of the ACE insertion/deletion polymorphism for the prognosis of type 2 diabetic subjects.
Published ahead of print at http://care.diabetesjournals.org on 3 June 2008.
M.M. and M.L. received funds from sanofi aventis for urinary albumin assays and data management for the DIABHYCAR study.
Details on the DIABHYCAR trial committees are available from previous publications (refs. 9 and 18).
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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