Prognostic Value of the Insertion/Deletion polymorphism of Angiotensin I Converting Enzyme gene in type 2 diabetic subjects: results from the DIABHYCAR, DIAB2NEPHROGENE & SURDIAGENE studies
- Samy HADJADJ, MD, PhD (s.hadjadj{at}chu-poitiers.fr)1,2,,
- Frédéric FUMERON, PhD3,,4,
- Ronan ROUSSEL, MD, PhD3,,4,,5,
- Pierre-Jean SAULNIER, MD6,
- Yves GALLOIS, PharmaD, PhD7,
- Amos ANKOTCHE, MD5,
- Florence TRAVERT, MD8,
- Charbel ABI KHALIL, MD3,,4,,5,
- Aurélie MIOT1,
- François ALHENC-GELAS, MD, PhD9,
- Michel LIEVRE, MD, PhD10 and
- Michel MARRE, MD, PhD on behalf of the DIABHYCAR, DIAB2NEPHROGENE & SURDIAGENE study groups3,,4,,5
- 1CHU Poitiers - Endocrinology, Diabetology, Poitiers, France
- 2INSERM, U927, Poitiers, France
- 3INSERM, U695, Xavier Bichat Faculty of Medicine, Paris, France
- 4Université Paris 7 Diderot, UFR Médecine Xavier Bichat, Paris, France
- 5Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Endocrinologie-Diabetologie-Nutrition, Paris, France
- 6CHU Poitiers, France – INSERM CIC 0802, Poitiers, France
- 7CHU Angers, Biochemistry, France
- 8Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, CIC Bichat, Paris, France
- 9INSERM, U652, Paris, France
- 10Université Claude Bernard Lyon 1, Faculté de Médecine Laënnec, Lyon, France
Abstract
Objective: We tested whether determining the Angiotensin I Converting Enzyme (ACE) Insertion/Deletion (I/D) polymorphism is useful for renal and cardiovascular prognoses of type 2 diabetic subjects.
Design: the French participants (3126 of the 4912) in the DIABHYCAR trial were studied for their prognosis over 4 years according to their ACE I/D polymorphism. We used 2 cohorts of French type 2 diabetic patients for replication: a 3-year follow-up study (n = 917, SURDIAGENE study) and a case-control study on diabetic nephropathy (n = 1277, DIAB2NEPHROGENE study). We investigated the effect of I/D polymorphism on primary outcome in the DIABHYCAR trial (first of the following events to occur: cardiovascular death, non-fatal myocardial infarction, stroke, heart failure leading to hospital admission, end-stage renal failure) and its components.
Results: In DIABHYCAR, primary outcome and most of its components were not affected by the ACE I/D 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 issue increased with the number of D alleles (p < 0.03). In SURDIAGENE, the association between ACE I allele and renal outcome was not replicated. In DIAB2NEPHROGENE, no association was found with nephropathy.
Conclusion: We were not able to demonstrate the manifest usefulness of ACE I/D polymorphism for the prognosis of type 2 diabetic subjects.
Footnotes
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- Received October 30, 2007.
- Accepted May 21, 2008.
- Copyright © American Diabetes Association
