title: Plasminogen activator inhibitor-1 and apolipoprotein E gene polymorphisms and diabetic angiopathy.
abstract: BACKGROUND
  A point mutation in the plasminogen activator inhibitor-1 (PAI-1) gene and a three-allelic variation in the apolipoprotein-E (ApoE) gene have been suggested as risk factors for the development of diabetic micro- and macrovascular complications.
  
  
  METHODS
  We studied 198 type 1 diabetic patients with diabetic nephropathy [121 men, age (mean+/-SD) 41+/-10 years, diabetes duration 28+/-8 years] and 192 patients with persistent normoalbuminuria (118 men, age 43+/-10 years, diabetes duration 27+/-9 years).
  
  
  RESULTS
  Male patients with nephropathy had elevated plasma PAI-1 levels [geometric mean (95% CI)], 70 (62-79) ng/ml, compared with normoalbuminuric men, 43 (38-47) ng/ml, P<0.001. Even though nephropathic patients with the 4G4G genotype tended to have higher plasma PAI-1 levels, P=0.06, no difference in allele frequency (4G/5G) was seen between patients with and without nephropathy: 0.538/0.462 vs 0.539/0.461, respectively. Nor did ApoE allele frequencies (epsilon2/epsilon3/epsilon4) differ between nephropathic and normoalbuminuric patients: 0.099/0.749/0. 152 vs 0.081/0.745/0.174, respectively. Genotype distributions were also similar, n.s. Coronary heart disease was more prevalent (36%) among nephropathic patients carrying the atherogenic epsilon4-allele compared with 12% in patients with the epsilon3,epsilon3 genotype, P<0.001. No associations between diabetic retinopathy and PAI-1 or ApoE polymorphisms were observed, n.s.
  
  
  CONCLUSIONS
  The ApoE polymorphism may accelerate the development of coronary heart disease often seen in Caucasian patients with type 1 diabetes and diabetic nephropathy, a condition characterized by elevated plasma PAI-1 in men. Neither the PAI-1 nor the ApoE gene polymorphism contributes to the genetic susceptibility to diabetic nephropathy or retinopathy.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Tarnow
authors.forename: C D
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: J J
authors.initials: JJ
authors.lastname: Emeis
authors.forename: O
authors.initials: O
authors.lastname: Poirier
authors.forename: F
authors.initials: F
authors.lastname: Cambien
authors.forename: B V
authors.initials: BV
authors.lastname: Hansen
authors.forename: H H
authors.initials: HH
authors.lastname: Parving
mesh_terms: D000328:Adult; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D003327:Coronary Disease / Q000235:genetics; D003922:Diabetes Mellitus, Type 1; D003925:Diabetic Angiopathies / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D001057:Apolipoproteins E; D017395:Plasminogen Activator Inhibitor 1