Mbs. Freire et al., DNA POLYMORPHISMS IN THE ACE GENE, SERUM ACE ACTIVITY AND THE RISK OFNEPHROPATHY IN INSULIN-DEPENDENT DIABETES-MELLITUS, Nephrology, dialysis, transplantation, 13(10), 1998, pp. 2553-2558
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.