The -7351C/T polymorphism in the TPA gene and ischemic stroke risk: a meta-analysis

PLoS One. 2013;8(1):e53558. doi: 10.1371/journal.pone.0053558. Epub 2013 Jan 9.


Background: A number of studies assessed the association of tissue plasminogen activator(TPA) gene polymorphisms with ischemic stroke, but the results were contradictory. We aimed to explore the role of TPA -7351C/T SNP in the susceptibility to ischemic stroke through a meta-analysis.

Methods: The PubMed, MEDLINE, EMBASE, China Biological Medicine Database and WANFANG DATA databases were searched until August 2012. The strict selection criteria and exclusion criteria were determined, and odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Stroke subtype was determined using Trial of Org 10172 in Acute Treatment criteria (TOAST). Statistical analyses were performed using the STATA12.0 software.

Results: A total of 2,299 ischemic stroke cases and 1,948 controls in seven case-control studies were included in the meta-analysis. Significant association between -7351C/T polymorphism in the TPA gene and ischemic stroke was observed in all comparison models (TT+CT versus CC, TT versus CT+CC and T versus C). In the subgroup analysis by ethnicity, TT homozygote carriers had a 142% increased risk of ischemic stroke compared with the C allele carriers among East-Asians (TT versus CT+CC: OR = 2.42, 95% CI = 1.07-5.48), but not in South-Asians and Caucasians, and significantly increased risks were found for T versus C among both East-Asians (OR = 1.33, 95% CI = 1.05-1.68) and Caucasians(OR = 1.16, 95% CI = 1.02-1.31). Further stratification for stroke subtype in three Caucasian studies showed the association between -7351C/T polymorphism and Large-artery atherosclerosis (LAA), but not Small-vessel occlusion (SVO) and Cardioembolism (CE).

Conclusions: This meta-analysis suggested that the -7351C/T polymorphism in TPA gene would be a risk factor for ischemic stroke, especially among East-Asians compared with Caucasians, but not in South-Asians, and it may play a role in the pathogenesis of LAA in Caucasians, but not in SVO and CE.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Ischemia / genetics*
  • Genetic Predisposition to Disease*
  • Humans
  • Models, Genetic
  • Polymorphism, Single Nucleotide / genetics*
  • Publication Bias
  • Risk Factors
  • Stroke / genetics*
  • Tissue Plasminogen Activator / genetics*


  • PLAT protein, human
  • Tissue Plasminogen Activator

Grants and funding

This study was supported by grants #81070912 from the National Natural Science Foundation of China and grant #2012BSA07022 from the Shandong Province Excellent Young Scientist Research Award Fund and grant #Z2012096 from Self-financing Science Foundation of Guangxi Health Bureau. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.