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.
OBJECTIVE
We tested whether determination of the ACE insertion/deletion polymorphism is useful for renal and cardiovascular prognoses of type 2 diabetic subjects.


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.
Centre Hospitalier Universitaire Poitiers, Endocrinology, Diabetology, Poitiers, France. s.hadjadj@chu-poitiers.fr
Samy
S
Hadjadj
Frédéric
F
Fumeron
Ronan
R
Roussel
Pierre-Jean
PJ
Saulnier
Yves
Y
Gallois
Amos
A
Ankotche
Florence
F
Travert
Charbel
C
Abi Khalil
Aurélie
A
Miot
François
F
Alhenc-Gelas
Michel
M
Lievre
Michel
M
Marre
D000368:Aged; D001794:Blood Pressure; D016022:Case-Control Studies; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D004251:DNA Transposable Elements; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D017384:Sequence Deletion
D004251:DNA Transposable Elements; D003404:Creatinine; D007703:Peptidyl-Dipeptidase A