Angiotensin-I converting enzyme insertion/deletion polymorphism and its association with diabetic nephropathy: a meta-analysis of studies reported between 1994 and 2004 and comprising 14,727 subjects.
OBJECTIVE
The ACE insertion/deletion polymorphism has been examined for association with diabetic nephropathy over the past decade with conflicting results. To clarify this situation, we conducted a comprehensive meta-analysis encompassing all relevant studies that were published between 1994 and 2004 and investigated this potential genetic association.


METHODS
A total of 14,727 subjects from 47 studies was included in this meta-analysis. Cases (n=8,663) were type 1 or 2 diabetic subjects with incipient (microalbuminuria) or advanced diabetic nephropathy (proteinuria, chronic renal failure, end-stage renal disease). Control subjects (n=6,064) were predominantly normoalbuminuric.


RESULTS
No obvious publication bias was detected. Using a minimal-case definition based on incipient diabetic nephropathy, subjects with the II genotype had a 22% lower risk of diabetic nephropathy than carriers of the D allele (pooled odds ratio [OR]=0.78, 95% CI=0.69-0.88). While there was a reduced risk of diabetic nephropathy associated with the II genotype among Caucasians with either type 1 or type 2 diabetes, the association was most marked among type 2 diabetic Asians (Chinese, Japanese, Koreans) (OR=0.65, 95% CI=0. 51-0.83). This OR is significantly different from the OR of 0.90 (95% CI= 0.78-1.04) that was obtained for type 2 diabetic Caucasians (p=0.019). Using a stricter case definition based on advanced diabetic nephropathy, a comparable risk reduction of 24-32% was observed among the three subgroups, although statistical significance was reached only among Asians.


CONCLUSIONS
The results of our meta-analysis support a genetic association of the ACE Ins/Del polymorphism with diabetic nephropathy. These findings may have implications for the management of diabetic nephropathy using ACE inhibitors especially among type 2 diabetic Asians.
Ng
D P K
DP
Department of Community, Occupational and Family Medicine, Faculty of Medicine (MD3), National University of Singapore, 16 Medical Drive, Singapore 117597, Singapore. cofnpkd@nus.edu.sg
Tai
B C
BC
Koh
D
D
Tan
K W
KW
Chia
K S
KS
D016022:Case-Control Studies; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004251:DNA Transposable Elements / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D006801:Humans; D016017:Odds Ratio; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics; D017384:Sequence Deletion
D004251:DNA Transposable Elements; D007703:Peptidyl-Dipeptidase A