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

  1. Samy Hadjadj, MD, PHD12,
  2. Frédéric Fumeron, PHD34,
  3. Ronan Roussel, MD, PHD345,
  4. Pierre-Jean Saulnier, MD6,
  5. Yves Gallois, PHARMD, PHD7,
  6. Amos Ankotche, MD5,
  7. Florence Travert, MD3458,
  8. Charbel Abi Khalil, MD345,
  9. Aurélie Miot, MSC1,
  10. François Alhenc-Gelas, MD, PHD9,
  11. Michel Lievre, MD, PHD10,
  12. Michel Marre, MD, PHD345 and
  13. on behalf of the DIABHYCAR, DIAB2NEPHROGENE, and SURDIAGENE study groups
  1. 1Centre Hospitalier Universitaire Poitiers, Endocrinology, Diabetology, Poitiers, France
  2. 2Institut National de la Santé et de la Recherche Médicale, U927, Poitiers, France
  3. 3Institut National de la Santé et de la Recherche Médicale, U695, Paris, France
  4. 4Unité de Formation et de Recherche Médecine Xavier Bichat, Université Paris 7 Diderot, Paris, France
  5. 5Endocrinologie-Diabetologie-Nutrition, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France
  6. 6Centre Hospitalier Universitaire Poitiers, France and Institut National de la Santé et de la Recherche Médicale, CIC 0802, Poitiers, France
  7. 7Biochemistry, Centre Hospitalier Universitaire, Angers, France
  8. 8CIC Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France
  9. 9Institut National de la Santé et de la Recherche Médicale, U652, Paris, France
  10. 10Faculté de Médecine Laënnec, Université Claude Bernard Lyon 1, Lyon, France
  1. Corresponding author: Samy Hadjadj, s.hadjadj{at}chu-poitiers.fr

Abstract

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.

Footnotes

  • 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.

    • Accepted May 21, 2008.
    • Received October 30, 2007.
« Previous | Next Article »Table of Contents

This Article

  1. Published online before print June 3, 2008, doi: 10.2337/dc07-2079 Diabetes Care September 2008 vol. 31 no. 9 1847-1852
  1. » Abstract
  2. Full Text
  3. Full Text (PDF)
  4. Online-Only Appendix
  5. All Versions of this Article:
    1. dc07-2079v1
    2. 31/9/1847 most recent

Current Issue

  1. March 2010, 33 (3)
  1. Current Issue
  1. Alert me to new issues of Diabetes Care