Dataset Information

Meta-analysis of the association between urokinase-plasminogen activator gene rs2227564 polymorphism and Alzheimer's disease.

ABSTRACT:

Objective

The association between urokinase-plasminogen activator (PLAU) gene rs2227564 polymorphism and Alzheimer's disease (AD) risk has been widely reported across different ethnic populations, with inconsistent results. Thus, we performed a meta-analysis to assess the association between PLAU rs2227564 polymorphism and AD risk.

Methods

Fixed or random effect model was used as the pooling method to assess the basis of homogeneity test among studies. Summarized estimation of odds ratio (OR) and 95% confidence interval (CI) were calculated. Heterogeneity among studies was evaluated using Q test and I (2). Publication bias was estimated using Harbord's test.

Results

A total of 27 studies (comprising 6100 AD cases and 5718 controls) were included in this meta-analysis. The present meta-analysis showed a significant increased effect of T allele on risk of AD in dominant model (fixed effect model [FEM] OR 1.123, 95% CI 1.025-1.231) and heterozygote comparison (CT vs CC; FEM OR 1.126, 95% CI 1.027-1.235). No publication bias was detected.

Conclusion

This meta-analysis showed that T allele of rs2227564 polymorphism in PLAU gene could increase the effects on risk of AD, and this result needs to be confirmed by further studies.

SUBMITTER: Wu W

PROVIDER: S-EPMC10852686 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature

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Publications

Meta-analysis of the association between urokinase-plasminogen activator gene rs2227564 polymorphism and Alzheimer's disease.

Wu Wenlong W Jiang Hong H Wang Meiyun M Zhang Dongfeng D

American journal of Alzheimer's disease and other dementias 20130628 5

<h4>Objective</h4>The association between urokinase-plasminogen activator (PLAU) gene rs2227564 polymorphism and Alzheimer's disease (AD) risk has been widely reported across different ethnic populations, with inconsistent results. Thus, we performed a meta-analysis to assess the association between PLAU rs2227564 polymorphism and AD risk.<h4>Methods</h4>Fixed or random effect model was used as the pooling method to assess the basis of homogeneity test among studies. Summarized estimation of odd ...[more]

PMID: 23813610

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Project description:Data from clinical studies, cell culture, and animal models implicate the urokinase (uPA)/Plasminogen (Plg) system in the development of atherosclerosis and aneurysms. However, the mechanisms through which uPA/Plg stimulate these diseases are not yet defined. We used genetically modified, atherosclerosis-prone mice, including mice with macrophage-specific uPA overexpression to clarify mechanisms of uPA/Plg-accelerated atherosclerosis and aneurysm formation. Microarray studies were performed to identify potential mediators of uPA-accelerated atherosclerosis. These studies identified S100A8 and S100A9 mRNA as the most highly upregulated transcripts in uPA-overexpressing macrophages; upregulation of S100A9 protein in uPA-overexpressing macrophages was confirmed by Western blotting. S100A8/A9, which are atherogenic in mice and are expressed in human atherosclerotic plaques, are also upregulated in aortae of mice with uPA-overexpressing macrophages, and macrophage S100A9 mRNA is upregulated by exposure of wild-type macrophages to medium from uPA-overexpressing macrophages. Bioinformatics analysis of the microarray data suggest significant effects of uPA overexpression on cell migration and cell-matrix interactions. Our results confirm—in a second animal model—that macrophage-expressed uPA stimulates atherosclerosis and aortic dilation. They also implicate specific pathways in uPA/Plg-accelerated atherosclerosis and aneurysmal disease. Six independent biological replicate RNA samples were prepared from thioglycollate-elicited peritoneal macrophages from mice of two different genotypes: SR-uPA+/0 transgenic (overexpress uPA in macrophages) and nontransgenic, respectively), for a total of 12 independent RNA samples. Both transgenic and nontransgenic mice were Apoe-/- and were fed Western diet from 5-15 weeks before peritoneal macrophages were elicited. In addition, from the six samples of each genotype, a pooled sample was prepared by combining the six genotype-specific samples. Each of the two pooled samples was assayed on the BeadChip in two technical replicates, for a total of 16 hybridizations performed using two Illumina Mouse Ref-8 v1.1 chips.

Dataset Information

Meta-analysis of the association between urokinase-plasminogen activator gene rs2227564 polymorphism and Alzheimer's disease.

Objective

Methods

Results

Conclusion

Publications

Meta-analysis of the association between urokinase-plasminogen activator gene rs2227564 polymorphism and Alzheimer's disease.

Similar Datasets

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