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中国人正常凝血因子抗凝血酶、蛋白 C 和蛋白 S 活性范围及其遗传变异。中国自然抗凝物调查 I 组研究结果。

Normal ranges and genetic variants of antithrombin, protein C and protein S in the general Chinese population. Results of the Chinese Hemostasis Investigation on Natural Anticoagulants Study I Group.

机构信息

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, 100730 Beijing, China.

出版信息

Haematologica. 2011 Jul;96(7):1033-40. doi: 10.3324/haematol.2010.037515. Epub 2011 Apr 12.

DOI:10.3324/haematol.2010.037515
PMID:21486865
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3128223/
Abstract

BACKGROUND

Inherited deficiency of antithrombin, protein C and protein S, three important, naturally occurring coagulation inhibitors, might play a major role in the occurrence of venous thromboembolism in Chinese. The establishment of age- and gender-related normal ranges of these inhibitors is crucial for an accurate diagnosis of these deficiencies.

DESIGN AND METHODS

We designed a prospective cross-sectional study recruiting healthy adults from four university-affiliated hospitals in China. Antithrombin, protein C and protein S were studied by measuring their activity. Gene analysis was performed when natural anticoagulant deficiency was suspected. Polymorphisms of the factor V gene were searched for among subjects who were positive for activated protein C resistance.

RESULTS

In 3493 healthy Chinese adults (1734 men, 1759 women; age 17-83 years), we found higher age-adjusted activities for protein C and protein S in men than in women but no sex difference for antithrombin. In women, mean protein C and protein S activities increased with age. In men, mean protein C levels increased with age up to the age of 49 but decreased after 50 years old; mean protein S levels decreased after 50 years of age. Antithrombin levels remained stable over time in women but decreased significantly after 50 years of age in men. Reference values according to age and sex allowed the identification of 15 genetic variants (protein C:10, antithrombin:3, protein S:2) in subjects with protein activity below the 1(st) percentile.

CONCLUSIONS

This is the largest survey ever conducted in the healthy general Chinese population. These normal ranges provide the essential basis for the diagnosis and treatment of thrombosis in Chinese.

摘要

背景

抗凝血酶、蛋白 C 和蛋白 S 是三种重要的天然抗凝抑制物,遗传性缺乏这些物质可能在中国人静脉血栓栓塞的发生中起主要作用。建立与年龄和性别相关的这些抑制剂的正常范围对于这些缺乏症的准确诊断至关重要。

设计和方法

我们设计了一项前瞻性的横断面研究,在中国的四家大学附属医院招募健康成年人。通过测量其活性来研究抗凝血酶、蛋白 C 和蛋白 S。当怀疑存在天然抗凝物缺乏时,进行基因分析。在对活化蛋白 C 抵抗呈阳性的受试者中,搜索因子 V 基因的多态性。

结果

在 3493 名健康的中国成年人(1734 名男性,1759 名女性;年龄 17-83 岁)中,我们发现男性的蛋白 C 和蛋白 S 活性校正后高于女性,但抗凝血酶无性别差异。在女性中,平均蛋白 C 和蛋白 S 活性随年龄增加而增加。在男性中,平均蛋白 C 水平随年龄增长至 49 岁,但 50 岁后下降;平均蛋白 S 水平在 50 岁后下降。女性的抗凝血酶水平随时间保持稳定,但男性在 50 岁后显著下降。根据年龄和性别确定的参考值可识别出蛋白活性低于第 1 百分位数的受试者中的 15 种遗传变异(蛋白 C:10、抗凝血酶:3、蛋白 S:2)。

结论

这是在中国健康普通人群中进行的最大规模的调查。这些正常范围为中国人血栓形成的诊断和治疗提供了必要的基础。

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