DNA POLYMORPHISMS IN THE ACE GENE, SERUM ACE ACTIVITY AND THE RISK OFNEPHROPATHY IN INSULIN-DEPENDENT DIABETES-MELLITUS

Background. To determine the relationship between DNA polymorphisms in the angiotensin I converting enzyme (ACE) gene, serum ACE activity an d the risk of diabetic nephropathy. Methods. A case-control study was carried out in a population of Jewish insulin-dependent diabetes melli tus (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 gen e: one in intron 7 detected with the restriction enzyme PstI and the o ther 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 ris k 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 activit y. Conclusions. The results of this study are evidence that the risk o f diabetic nephropathy in IDDM is influenced by genetic variability at the ACE locus, but the responsible Variant is not the I/D polymorphis m in intron 16. Our findings require further studies in other populati ons.