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- Title
Association between high von Willebrand factor levels and the Thr789Ala vWF gene polymorphism but not with nephropathy in type I diabetes.
- Authors
Lacquemant, Corinne; Gaucher, Christine; Delorme, Catherine; Chatellier, Gilles; Gallois, Yves; Rodier, Michel; Passa, Philippe; Balkau, Beverley; Mazurier, Claudine; Marre, Michel; Froguel, Philippe
- Abstract
Association between high von Willebrand factor levels and the Thr789Ala vWF gene polymorphism but not with nephropathy in type I diabetes. 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...
- Subjects
EUROPE; PEOPLE with diabetes; VON Willebrand factor; KIDNEY diseases
- Publication
Kidney International, 2000, Vol 57, Issue 4, p1437
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2000.00988.x