Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Low protein Z levels and risk of ischemic stroke: differences by diabetic status and gender. 1249 Feb 80

Protein Z (PZ) is a single chain vitamin-K-dependent glycoprotein synthesized by the liver. Studies in vivo and in vitro suggest that PZ plays an important role in inhibiting coagulation as it serves as cofactor for the inactivation of factor Xa by forming a complex with the plasma PZ-dependent protease inhibitor. Recently, conflicting findings on plasma PZ levels in patients with ischemic stroke have been published. Aim of our study was to investigate the role of PZ in acute coronary syndromes (ACS). PZ plasma levels were determined in 223 (189 M; 34 F) patients with ACS referring to the Coronary Intensive Therapy Unit of University of Florence and in 265 (219 M; 46 F) healthy subjects. Patients under oral anticoagulation treatment as well as subjects with positivity for antiphospholipid antibodies were excluded. None had liver or kidney dysfunction. The mean PZ plasma level was lower in patients (1508 +/- 730 ng/mL) than in controls (1728 +/- 594 ng/mL) (p < 0.0001). PZ levels below the 5th percentile (565 ng/mL) of normal values distribution in control subjects were found in 15.7% of patients and in 4.9% of controls (p <0.0001). At multivariate analysis, PZ levels below 565 ng/mL were associated with ACS (OR=3.3; 99%CI 1.1-9.7; p = 0.004). The contemporary presence of low PZ levels and smoking habit leads to an increased risk of ACS (OR=9.5; 99%CI 2.4-37.2; p < 0.0001). In conclusion, our results suggest a possible role of PZ in the occurrence of arterial thrombosis.
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PMID:Low protein Z plasma levels are independently associated with acute coronary syndromes. 1465 53

Protein Z (PZ) is a vitamin K-dependent plasma glycoprotein that acts as a cofactor for PZ-dependent protease inhibitor to inhibit coagulation factor X(a). Studies in mice suggest that that decreased blood PZ levels lead to reduced inhibition of blood coagulation, thereby predisposing to thrombosis; however, clinical studies in humans have yielded conflicting results. Among patients with stroke, some epidemiologic studies have reported that reduced PZ levels increase the risk of stroke, whereas others have reported no association between PZ levels and stroke, or that elevated PZ levels increase stroke risk. Polymorphisms involving the gene for PZ can influence the PZ concentration and some polymorphisms (eg, intron G79A AA allele) may be protective against stroke, particularly among younger individuals. Although the association between PZ levels and stroke appears to be stronger in younger patients and in patients who do not have conventional vascular risk factors, it remains unclear whether the link between PZ levels and stroke is confounded or causal or whether blood levels of PZ are altered as a consequence of the acute stroke event.
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PMID:Role of protein z in stroke. 1760 82

Protein Z (PZ) is a vitamin K-dependent factor identified in human plasma in 1984 characterized by an homology with other vitamin K-dependent factors (factor VII, IX, X, protein C). In contrast to these factors, PZ does not possess any enzymatic activity but is involved as a cofactor in the down-regulation of coagulation by forming a complex with the protein Z-dependent protease inhibitor (ZPI). ZPI inhibits the activated factor X (FXa) on phospholipid surface. In mice, the disruption of PZ gene is asymptomatic, but the association with the factor V Leiden mutation leads to a quasi complete mortality during the neonatal period with microvascular thrombosis. In humans, PZ is characterized by an unusual wide distribution in plasma, and a major decrease induced by warfarin. Isolated PZ deficiency does not seem to constitute a risk for venous thrombosis, but a severe PZ deficiency could increase the risk of well recognized venous thrombotic risk factors such as factor V Leiden, G20210A mutation or hyperhomocysteinemia. Unexpectedly, a relationship between PZ deficiency and ischemic arterial diseases such as stroke, acute coronary syndromes or peripheral arterial disease was described but not confirmed by all studies. PZ deficiency could be also a risk factor for early fetal losses, and increases the arterial risk in antiphospholipid syndrome. This review analyzes the different studies so far published and discusses the various results obtained in order to understand whether or not protein Z deficiency could be considered as an arterial ischemic risk factor.
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PMID:Protein Z, a protein seeking a pathology. 1884 Dec 75