血管性血友病因子水平升高与I型糖尿病患者中血管性血友病因子（vWF）基因Thr789Ala多态性相关，但与肾病无关。GENEDIAB研究组和DESIR研究组。

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.

作者信息

Lacquemant C, Gaucher C, Delorme C, Chatellier G, Gallois Y, Rodier M, Passa P, Balkau B, Mazurier C, Marre M, Froguel P

机构信息

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.

出版信息

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

DOI:10.1046/j.1523-1755.2000.00988.x

PMID:10760079

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.

摘要

背景

由于仅30%至40%的I型糖尿病患者会发生糖尿病肾病，因此怀疑存在糖尿病肾病的遗传易感性。由于据报道I型糖尿病患者血浆中血管性血友病因子（vWF）浓度升高先于微量白蛋白尿的发生，我们探讨了vWF作为糖尿病肾病遗传决定因素的可能影响。

方法

对一组493名I型糖尿病患者的三种已知vWF基因多态性进行基因分型，所有患者均表现为增殖性视网膜病变，但肾脏受累程度不同，从无微量白蛋白尿（尽管糖尿病平均病程为31年）到晚期肾病（GENEDIAB研究）：Thr789Ala（Rsa I）、M-/M+（Msp I）（内含子19）和Ala1381Thr（Hph I）。还测量了该人群的血浆vWF和因子VIII（F VIII）水平。

结果

患有肾病（P < 0.001）或冠心病（CHD；P < 0.001）的糖尿病患者血浆vWF和F VIII水平升高，但两种情况对血浆水平没有相互作用。Msp I多态性（M-/M+）与肾病弱相关（P = 0.04），但在逻辑回归分析中使用其他危险因素时，这种相关性并不更显著。vWF Thr789Ala多态性与CHD（P = 0.002）和血浆vWF水平相关。逻辑回归分析表明，Thr789Ala多态性对CHD有独立的共显性影响，但对肾病没有影响，Ala/Ala纯合子的风险最大（OR = 4.2，95% CI，1.8至9.9，P = 0.0008）。