Low Protein Z Levels and Risk of Ischemic Stroke: Differences by Diabetic Status and Gender

Heeb, Mary J.; Paganini‐Hill, Annlia; Griffin, John H.; Fisher, Mark

doi:10.1006/bcmd.2002.0549

Cited by 65 publications

(87 citation statements)

References 14 publications

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“…However, previous studies were performed primarily in younger stroke patients and in different ethnic populations. [7][8][9][10][11][12] Because genetic factors may play a disproportionately greater role in the cause and pathogenesis of stroke in selected younger patients and in certain ethnic populations and are also important determinants of protein Z concentrations in the blood, genetic differences may account for some of the disagreement between the studies. A strength of our study was that we included a broad range of patients with stroke who were compared with randomly selected community based controls, matched for age, sex, and postal code.…”

Section: Discussionmentioning

confidence: 99%

“…However, epidemiological studies report conflicting associations between protein Z concentrations in the blood and bleeding or thrombotic phenotype, 3,4 and risk of acute coronary syndrome 5,6 or stroke. [7][8][9][10][11][12] Among patients with stroke, some studies suggest that reduced blood concentrations of protein Z increase stroke risk, [7][8][9] whereas others suggest no association 10 or that increased concentrations increase stroke risk. 11,12 We recently demonstrated that increased blood concentrations of protein Z measured during the first 7 days after the acute event were independently associated with ischemic stroke, but this association was no longer evident during the convalescent phase 3 to 6 months after the event.…”

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confidence: 99%

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Protein Z Gene Polymorphisms, Protein Z Concentrations, and Ischemic Stroke

Staton

Sayer

Hankey

et al. 2005

Stroke

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Background and Purpose-We aimed to determine whether A-13G or G79A polymorphisms of the protein Z gene that have been reported to be an important determinant of blood concentrations of protein Z are associated with risk of ischemic stroke in a broad range of stroke patients and controls. Methods-We conducted a case control study of 151 hospital cases of first-ever ischemic stroke and 164 randomly selected community controls. Protein Z genotype was determined for the A-13G promoter polymorphism and the G79A intron F polymorphism, and plasma protein Z concentrations were measured during the first 7 days and at 3 to 6 months after the acute stroke event. Results-Geometric mean concentrations of protein Z measured within 7 days of acute stroke were significantly higher in cases compared with controls (1.51 g/mL versus 1.13 g/mL; PϽ0⅐0001). Protein Z concentrations were highest among subjects with the A-13G AA genotype, intermediate among those with the AG genotype, and lowest among those with the GG genotype (1.39 g/mL versus 1.05 g/mL versus 0.76 g/mL; PϽ0.0001); and highest among those with the G79A GG genotype, intermediate among those with the GA genotype, and lowest among those with the AA genotype (1.47 g/mL versus 1.13 g/mL versus 0.66 g/mL; PϽ0.0001). The prevalence of A-13G and G79A genotypes was not significantly different between cases of ischemic stroke and controls. However, compared with the G79A GG genotype (reference), the odds of ischemic stroke was progressively lower for the heterozygote GA (odds ratio [OR], 0.83; 95% CI, 0.52 to 1.33) and the homozygote AA genotype (OR, 0.63; 95% CI, 0.20 to 1.98). A pooled analysis showed that compared with the G79A GG genotype (reference), the odds of ischemic stroke was progressively lower for the heterozygote GA (OR, 0.78; 95% CI, 0.57 to 1.07) and the homozygote AA genotype (OR, 0.31; 95% CI, 0.14 to 0.69). Conclusion-The consistency of the association between protein Z genotypes, blood concentrations of protein Z, and ischemic stroke, determined using 2 different methods that have different sources of bias strengthens the evidence that increased blood concentrations of protein Z concentrations are associated causally with an increased risk of ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Protein Z Gene Polymorphisms, Protein Z Concentrations, and Ischemic Stroke

Staton

Sayer

Hankey

et al. 2005

Stroke

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“…Whereas Kobelt and colleagues 11 described a significant association of high plasma levels of PZ with cryptogenic stroke, Vasse and colleagues 12 found decreased levels in juvenile patients with cerebral ischemia. Another study by Heeb et al 13 performed in an elderly population also depicted an association of low PZ and risk of stroke, but this finding was restricted to nondiabetic males. The study by Hankey et al 14 was the only one that investigated PZ levels in the acute stage of cerebral ischemia.…”

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confidence: 90%

A Common Polymorphism of the Protein Z Gene Is Associated With Protein Z Plasma Levels and With Risk of Cerebral Ischemia in the Young

Lichy

Kropp

Dong‐Si

et al. 2004

Stroke

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Background and Purpose-The vitamin K-dependent protein Z (PZ) has been shown to possess anticoagulant as well as procoagulant properties. Plasma levels of PZ show a broad interindividual variation, but it is unknown to which extent this variation is under genetic control. Recent clinical studies revealed contradictory results on the association of PZ plasma levels and the risk of ischemic stroke. Methods-We performed a case-control study including 200 patients with cerebral ischemia aged Յ50 years and 199 control subjects from the same South German region. We investigated a possible association of 2 common single nucleotide mutations in the PZ gene with the risk of cerebral ischemia. Furthermore, enzyme-linked immunosorbent assay measurements were done in control subjects without vascular disease to detect a potential association of different genotypes with PZ plasma (antigen) levels. Results-In patients, the frequency of the A allele of the intron F polymorphism G79A was significantly lower than in controls (15.7% versus 24.4%; odds ratio, 0.58; 95% CI, 0.39 to 0.86; Pϭ0.007; adjusted for age, sex, and conventional risk factors). The G allele of the promoter polymorphism A-13G tended to be less common in patients (4.2% versus 7.0%; adjusted odds ratio, 0.56; 95% CI, 0.28 to 1.13; Pϭ0.105). In 42 control subjects, the A allele of the intron F polymorphism was associated with lower PZ antigen levels (Pϭ0.0032; Spearman correlation coefficient r s ϭϪ0.48). Conclusions-The

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“…Despite its large use, there are concerns about the efficacy of aspirin and methods to evaluate it [2,3]. Indeed, it appears that the antiplatelet effect of aspirin is not uniform in all patients and previous studies estimated that 8-45% of the population were aspirin resistant [4][5][6][7][8]. Most studies have focused on patients with coronary artery disease, although a few reports have identified aspirin resistance in patients with stroke or cerebrovascular disease [6][7][8][9].…”

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confidence: 99%