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

Kidney Int. 2000 Apr;57(4):1437-43. doi: 10.1046/j.1523-1755.2000.00988.x.


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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Coronary Disease / blood
  • Coronary Disease / genetics
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetic Angiopathies / blood
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / genetics
  • Factor VIII / analysis
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Polymorphism, Genetic / genetics*
  • Reference Values
  • von Willebrand Factor / analysis*
  • von Willebrand Factor / genetics*


  • von Willebrand Factor
  • Factor VIII