Heeb Mary J, Paganini-Hill Annlia, Griffin John H, Fisher Mark
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Blood Cells Mol Dis. 2002 Sep-Oct;29(2):139-44. doi: 10.1006/bcmd.2002.0549.
Protein Z was recently shown to act as an essential cofactor for protein Z-dependent protease inhibitor, a potent downregulator of coagulation Factor Xa. Thus, deficiency of protein Z is hypothesized to lead to a prothrombotic state, but two publications reported opposing results for the relationship of protein Z levels with ischemic stroke in young European subjects (mean age 33-40 years). We performed a study of stroke in a different ethnic population of greater mean age (57 years) to further clarify this issue. An ELISA was developed to measure protein Z antigen in 154 patients with ischemic stroke and in 206 controls in a largely Hispanic population. Low plasma protein Z values were significantly associated with ischemic stroke except in diabetic subjects and females. The mean protein Z value was significantly lower in stroke cases than in controls for nondiabetic subjects [1.78 +/- 0.77 (S.D.) versus 2.28 +/- 0.88 microg/ml, P < 0.0001] and for males (1.90 +/- 0.90 versus 2.42 +/- 0.99 microg/ml, P = 0.0004). Stroke risk was higher in subjects with protein Z levels at or below the fifteenth percentile of controls (</=1.46 microg/ml). The odds ratios were: 2.6 for all subjects (95% C.I. = 1.5-4.3); 3.8 for nondiabetic subjects (95% C.I. = 2.2-6.8); and 3.6 for males (95% C.I. = 2.0-6.4). This study also revealed high protein Z levels associated with high triglyceride levels in controls (P = 0.015). Protein Z is suggested to be a physiologic downregulator of blood coagulation and low protein Z levels are associated with increased risk of ischemic stroke, particularly in males and in the absence of diabetes.
最近研究表明，蛋白Z是蛋白Z依赖性蛋白酶抑制剂的一种必需辅助因子，该抑制剂是凝血因子Xa的一种强效下调因子。因此，推测蛋白Z缺乏会导致血栓形成倾向，但有两篇论文报道了欧洲年轻受试者（平均年龄33 - 40岁）中蛋白Z水平与缺血性中风关系的相反结果。我们在平均年龄更大（57岁）的不同种族人群中开展了一项中风研究，以进一步阐明这一问题。我们开发了一种酶联免疫吸附测定法（ELISA），用于测量154例缺血性中风患者和206名对照者（主要为西班牙裔人群）的蛋白Z抗原。除糖尿病患者和女性外，低血浆蛋白Z值与缺血性中风显著相关。非糖尿病患者中风病例的平均蛋白Z值显著低于对照组[1.78±0.77（标准差）对2.28±0.88微克/毫升，P < 0.0001]，男性也是如此（1.90±0.90对2.42±0.99微克/毫升，P = 0.0004）。蛋白Z水平处于或低于对照组第十五百分位数（≤1.46微克/毫升）的受试者中风风险更高。优势比分别为：所有受试者为2.6（95%置信区间 = 1.5 - 4.3）；非糖尿病受试者为3.8（95%置信区间 = 2.2 - 6.8）；男性为3.6（95%置信区间 = 2.0 - 6.4）。该研究还揭示，对照组中高甘油三酯水平与高蛋白Z水平相关（P = 0.015）。提示蛋白Z是血液凝固的生理性下调因子，低蛋白Z水平与缺血性中风风险增加相关，尤其是在男性和无糖尿病的情况下。
