Abstract
BackgroundA 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.MethodsThe 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.ResultsA 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).ConclusionsThis 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.
Highlights
The coagulation system and fibrinolysis system maintain a dynamic equilibrium under normal conditions
Thrombosis is a critical event in the arterial diseases associated with ischemic stroke [2], so any factors that influence the critical balance within the fibrinolysis system may be of particular relevance to the risk of ischemic stroke
The selected studies had to be in accordance with the following major criteria: a) well-designed case-control studies to evaluate the association between tissue plasminogen activator (TPA) -7351C/T and ischemic stroke, b) ischemic stroke was confirmed by neuroimaging data, c) containing useful genotype frequencies, d) the genotype distribution of controls in Hardy-Weinberg equilibrium (HWE)
Summary
The coagulation system and fibrinolysis system maintain a dynamic equilibrium under normal conditions. Stratification for stroke subtype showed the association between the polymorphism and lacunar infarction (OR = 2.70; 95% CI = 1.10–6.70), but not other subtypes [6], yet other studies failed to replicate it [7,8,9,10,11,12] Many of these studies used relatively small sample sizes, and such studies may have missed true associations of modest effect, so a meta-analysis of these results is needed to explore the inconsistencies. 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
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