Nephrol Dial Transplant (2000) 15: 625-630
© 2000 European Renal Association-European Dialysis and Transplant Association
Plasminogen activator inhibitor-1 and apolipoprotein E gene polymorphisms and diabetic angiopathy
1 Steno Diabetes Center, Gentofte, Denmark, 2 University Hospital and Institute for Cardiovascular Research Vrije Universiteit, Amsterdam, The Netherlands, 3 Gaubius Laboratory, TNO PG, Leiden, The Netherlands and 4 INSERM U525, Paris, France
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 (
2/3/4) 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 4-allele compared with 12% in patients with the 3,3 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.
Keywords: ApoE polymorphism; coronary heart disease; diabetic complications; diabetic nephropathy; PAI-1 polymorphism; type 1 diabetes
Correspondence and offprint requests to: Lise Tarnow, MD, Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark.
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