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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 Centre Hospitalier Universitaire Poitiers, Endocrinology, Diabetology, Poitiers, France
² Institut National de la Santé et de la Recherche Médicale, U927, Poitiers, France
³ Institut National de la Santé et de la Recherche Médicale, U695, Paris, France
⁴ Unité de Formation et de Recherche Médecine Xavier Bichat, Université Paris 7 Diderot, Paris, France
⁵ Endocrinologie-Diabetologie-Nutrition, Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France
⁶ Centre Hospitalier Universitaire Poitiers, France and Institut National de la Santé et de la Recherche Médicale, CIC 0802, Poitiers, France
⁷ Biochemistry, Centre Hospitalier Universitaire, Angers, France
⁸ CIC Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France
⁹ Institut National de la Santé et de la Recherche Médicale, U652, Paris, France
¹⁰ Faculté de Médecine Laënnec, Université Claude Bernard Lyon 1, Lyon, France

Corresponding author: Samy Hadjadj, s.hadjadj{at}chu-poitiers.fr

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.

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				D. P.K. Ng 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: Response to Hadjadj et al. Diabetes Care, October 1, 2008; 31(10): e78 - e78. [Full Text] [PDF]

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