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Kidney Int. 2000 Apr;57(4):1437-43.

Association between high von willebrand factor levels and the Thr789Ala vWF gene polymorphism but not with nephropathy in type I diabetes. The GENEDIAB Study Group and the DESIR Study Group.

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1
Laboratoire de Génétique des Maladies Multifactorielles, CNRS UPRES A 8090, Institut de Biologie de Lille, and Laboratoire Français du Fractionnement et des Biotechnologies, Lille; Arras Hospital; Medical Informatics, Broussais Hospi.

Abstract

BACKGROUND:

A genetic susceptibility for diabetic kidney disease is suspected since diabetic nephropathy occurs in only 30 to 40% of type I diabetic patients. As elevated von Willebrand factor (vWF) plasma concentrations have been reported to precede the development of microalbuminuria in type I diabetes, we addressed a possible implication of vWF as a genetic determinant for diabetic nephropathy.

METHODS:

Three known vWF gene polymorphisms were genotyped in a group of 493 type I diabetic subjects, all showing proliferative retinopathy, but with various stages of renal involvement, which ranged from no microalbuminuria, despite a mean duration of diabetes of 31 years, to advanced nephropathy (GENEDIAB Study): Thr789Ala (Rsa I), M-/M+ (Msp I) (intron 19), and Ala1381Thr (Hph I). Plasma vWF and factor VIII (F VIII) levels were also measured in this population.

RESULTS:

Plasma vWF and F VIII levels were increased in diabetic subjects with nephropathy (P < 0.001) or with coronary heart disease (CHD; P < 0.001), but there was no interaction of both conditions on plasma levels. The Msp I polymorphism (M-/M+) was weakly associated with nephropathy (P = 0. 04), but this association was not more significant when other risk factors were used in a logistic regression analysis. The vWF Thr789Ala polymorphism was associated with CHD (P = 0.002) and with plasma vWF levels. Logistic regression analysis indicated an independent and codominant effect of the Thr789Ala polymorphism on CHD, but not on nephropathy, with a maximal risk for Ala/Ala homozygotes (OR = 4.2, 95% CI, 1.8 to 9.9, P = 0.0008).

CONCLUSION:

It is unlikely that polymorphisms in the vWF gene contribute to the risk for nephropathy in type I diabetic patients. However, the Thr789Ala polymorphism might affect the risk for CHD in this population through modulation of plasma vWF levels.

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