Kamphuisen P W, Houwing-Duistermaat J J, van Houwelingen H C, Eikenboom J C, Bertina R M, Rosendaal F R
Hemostasis and Thrombosis Research Center and the Department of Medical Statistics, Leiden University Medical Center, The Netherlands.
Thromb Haemost. 1998 Feb;79(2):323-7.
Recently, we found that high levels of clotting factor VIII (>150 IU/dl) are common and make an important contribution to thrombotic risk. The determinants of high factor VIII:C are unclear and might be partly genetic. Therefore, we tested the influence of age, blood group and von Willebrand factor (VWF) levels on factor VIII:C levels, and investigated whether factor VIII:C levels are genetically determined. We performed an analysis of 564 female relatives of hemophilia A patients, who had visited our center for genetic counseling. In univariate analysis, AB0 blood group, age and VWF antigen (VWF:Ag) levels all influenced factor VIII:C levels. After adjustment for the effect of VWF:Ag levels, both blood group and age still had an effect on factor VIII:C levels. In sister pairs, the Pearson correlation coefficient between factor VIII:C levels was 0.17 (p = 0.024) and this correlation remained positive (0.15, p = 0.046) after correction for the influence of VWF:Ag. In mother-daughter pairs, no correlation of factor VIII:C levels was found. The correlation of VWF:Ag levels in sisterpairs was 0.41 (p <0.001) and in mother-daughter pairs 0.44 (p <0.001), in line with the assumption that VWF:Ag levels are under control of autosomal genes. Familial influence on plasma factor VIII:C and VWF:Ag levels was investigated with a recently developed familial aggregation test. This test verifies whether familial aggregation of a particular parameter exists in a set of pedigrees. In 435 women from 168 families, factor VIII:C as well as VWF:Ag levels correlated significantly within families, which suggests a familial influence. The familial aggregation was more prominent for VWF:Ag levels than for factor VIII:C levels, possibly because the genetic effect on VWF:Ag levels is larger than on factor VIII:C levels. Our results support the presence of a familial influence on factor VIII:C as well as on VWF:Ag levels.
最近，我们发现高水平的凝血因子VIII（>150 IU/dl）很常见，并且对血栓形成风险有重要影响。高因子VIII：C的决定因素尚不清楚，可能部分是由基因决定的。因此，我们测试了年龄、血型和血管性血友病因子（VWF）水平对因子VIII：C水平的影响，并研究了因子VIII：C水平是否由基因决定。我们对564名因遗传咨询前来我们中心就诊的甲型血友病患者的女性亲属进行了分析。在单变量分析中，ABO血型、年龄和VWF抗原（VWF：Ag）水平均影响因子VIII：C水平。在调整VWF：Ag水平的影响后，血型和年龄对因子VIII：C水平仍有影响。在姐妹对中，因子VIII：C水平之间的Pearson相关系数为0.17（p = 0.024），在校正VWF：Ag的影响后，这种相关性仍然为正（0.15，p = 0.046）。在母女对中，未发现因子VIII：C水平的相关性。姐妹对中VWF：Ag水平的相关性为0.41（p <0.001），母女对中为0.44（p <0.001），这与VWF：Ag水平受常染色体基因控制的假设一致。我们使用最近开发的家族聚集试验研究了家族对血浆因子VIII：C和VWF：Ag水平的影响。该试验验证了一组家系中是否存在特定参数的家族聚集。在168个家庭的435名女性中，因子VIII：C以及VWF：Ag水平在家族内显著相关，这表明存在家族影响。VWF：Ag水平的家族聚集比因子VIII：C水平更明显，可能是因为基因对VWF：Ag水平的影响大于对因子VIII：C水平的影响。我们的结果支持家族对因子VIII：C以及VWF：Ag水平有影响。
