Journal Article

Plasminogen activator inhibitor‐1 and apolipoprotein E gene polymorphisms and diabetic angiopathy

Lise Tarnow, Coen D. A. Stehouwer, Jef J. Emeis, Odette Poirier, François Cambien, Birgitte V. Hansen and Hans‐Henrik Parving

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 15, issue 5, pages 625-630
Published in print May 2000 | ISSN: 0931-0509
Published online May 2000 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/15.5.625
Plasminogen activator inhibitor‐1 and apolipoprotein E gene polymorphisms and diabetic angiopathy

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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 (ε2/ε3/ε4) 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 ε4‐allele compared with 12% in patients with the ε3,ε3 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

Journal Article.  4518 words. 

Subjects: Nephrology

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