title: DNA polymorphisms in the ACE gene, serum ACE activity and the risk of nephropathy in insulin-dependent diabetes mellitus.
abstract: 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 mellitus (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.
authors.affiliation: Joslin Diabetes Centre, Department of Medicine, Harvard Medical School Boston, Massachusetts 02215, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Freire
authors.forename: D J
authors.initials: DJ
authors.lastname: van Dijk
authors.forename: A
authors.initials: A
authors.lastname: Erman
authors.forename: G
authors.initials: G
authors.lastname: Boner
authors.forename: J H
authors.initials: JH
authors.lastname: Warram
authors.forename: A S
authors.initials: AS
authors.lastname: Krolewski
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D004247:DNA / Q000032:analysis*; D015342:DNA Probes / Q000737:chemistry; D004251:DNA Transposable Elements / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000201:enzymology*; D003928:Diabetic Nephropathies / Q000201:enzymology* / Q000209:etiology; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D015342:DNA Probes; D004251:DNA Transposable Elements; D004247:DNA; D007703:Peptidyl-Dipeptidase A