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Nephrology Dialysis Transplantation, Vol 13, Issue 10 2553-2558, Copyright © 1998 by Oxford University Press

ORIGINAL ARTICLES

DNA polymorphisms in the ACE gene, serum ACE activity and the risk of nephropathy in insulin-dependent diabetes melitus

M Freire, D van Dijk, A Erman, G Boner, J Warram and A Krolewski
Research Division, Joslin Diabetes Centre and Department of Medicine, One Joslin Place, Boston, MA 02215, USA; Institute of Hypertension and Kidney Diseases, Rabin Medical Centre, Beilinson Medical Centre, Petach Tikwa and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Current address: Faculdade de Medicina de Jundiai, Jundiai, Brazil; Corresponding author

Background. To determine the relationship between DNA polymorphisms in the angiotensin I converting enzyme (ACE) gene, serum ACE activity and the risk of diabetic nephropathy. Methods. A case-control study was carried out in a population of Jewish insulin-dependent diabetes melitus (IDDM) patients. Cases (77 IDDM patients with diabetic nephropathy) and controls (89 IDDM patients with normoalbuminuria) were genotyped with PCR protocols for detecting two DNA polymorphisms in the ACE gene: one in intron 7 detected with the restriction enzyme PstI and the other in intron 16 identified as an insertion/deletion (I/D). Results. The risk of nephropathy was increased only in patients homozygous for the allele with the PSTI site. These homozygotes had a nephropathy risk that was 2.3 times (95% C.I.: 1.2-4.5) that of the other genotypes. Furthermore, these individuals did not have elevated serum ACE activity. Conclusions. The results of this study are evidence that the risk of diabetic nephropathy in IDDM is influenced by genetic variability at the ACE locus, but the responsible variant is not the I/D polymorphism in intron 16. Our findings require further studies in other populations.
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