Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of ischemic stroke: a meta-analysis

Abstract

This study investigated the hypothesis that the insertion/deletion (4G/5G) polymorphism of the plasminogen activator inhibitor type-1 gene affects the risk for ischemic stroke, since results concerning this association have been controversial. We therefore performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out until January 2006. The analysis was performed using random-effects models and meta-regression. Eighteen eligible studies were retrieved (15 case-control studies and three cohort studies). The case-control studies included 3104 cases and 4870 control individuals concerning the contrast of 4G/4G versus remaining genotypes. The 4G pooled allele frequencies in cases and controls were 54.21 and 54.75%, respectively. Overall, the per-allele odds ratio of the 4G allele was 0.98 (95% confidence interval, 0.858-1.121). Regarding genotypes, we derived nonsignificant odds ratios in all contrasts. The subanalysis including the three studies with a prospective design in the 4G/4G versus 5G/5G contrast derived a significant result (relative risk, 0.523; 95% confidence interval, 0.353-0.775), but the estimated effect size was insignificant when cohort and case-control studies were analyzed together (relative risk, 0.848; 95% confidence interval, 0.662-1.087). We failed to demonstrate a significant association between the 4G/5G polymorphism and ischemic stroke under basal conditions. Determination of plasminogen activator inhibitor type-1 function seems of much higher clinical value than determination of the 4G/5G polymorphism. The effect of this genotype on risk of ischemic stroke in acute stressful diseases and the role of cohort studies in genetic epidemiology, however, warrant further investigation.

The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G/5G polymorphism, and myocardial infarction: a Mendelian randomization meta-analysis

“…This is in accordance with the findings of a recent meta-analysis that reported a positive association between the PAI-1 4G genotype and cardiac disease but a lack of relationship with stroke [14]. Similarly, we did not demonstrate a significant association between the 4G/5G polymorphism and ischemic stroke under basal conditions [99]. Stroke is not as clearly related to MetS as CAD is.…”

Specific Polymorphism 4G/5G Gene for PAI-1 as a Possible Cause of Cerebral Venous Thrombosis: A Case Report

“…In addition, it was shown that in most cases the contribution of PAI-1 4G/5G polymorphism of the synergetic conditioned by the presence of other congenital and/or acquired conventional risk factors for the occurrence of arterial, and venous thrombosis, such as hypertension, diabetic disease, obesity, malignant diseases, chronic inflammatory diseases, hereditary hyper coagulopathy and similar (1-4), which also can have a significant impact on the level of PAI-1 in plasma. In contrast, none of the previous studies have established significant connection 4G/5G genotype and ischemic stroke (20,21). Moreover, in contrast to the thrombosis of the coronary arteries which is dominated by allelic variant 4G with the increase of PAI-1 in plasma, cerebral artery thrombosis is significantly associated only with the homozygous genotype 5G/5G, accompanied by a reduced plasma levels of PAI-1 (8).…”

Thrombophilic Abnormalities in Patients With or Without Pulmonary Embolism Following Elective Spinal Surgery

“…Plasminogen activator inhibitor-1 4G/5G heterozygous mutation was detected, in the present study, in eight (66.7%) in the PE group and six (50%) in the control group. In the meta-analysis the frequency of the 4G/5G heterozygous mutation was 52.2% in the case group and 47.9 in the control group [15].…”

“…In the literature, a meta-analysis with 22 articles by Tsantes et al [15]. disclosed the frequency of the 4G/4G homozygous mutation in 29.0% (767 of 2,644 patients) in the case group (DVT or DVT + PE) and 24.0% (897 of 3,739 patients) in the control group, indicating the lack of striking difference.…”