title: 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.
authors.affiliation: Laboratory of Hematology and Blood Bank Unit, 'Attikon' General Hospital, School of Medicine, University of Athens, Athens, Greece.
authors.forename: Argirios E
authors.initials: AE
authors.lastname: Tsantes
authors.forename: Georgios K
authors.initials: GK
authors.lastname: Nikolopoulos
authors.forename: Pantelis G
authors.initials: PG
authors.lastname: Bagos
authors.forename: Chrissa G
authors.initials: CG
authors.lastname: Tsiara
authors.forename: Violetta
authors.initials: V
authors.lastname: Kapsimali
authors.forename: Anthi
authors.initials: A
authors.lastname: Travlou
authors.forename: Georgios
authors.initials: G
authors.lastname: Vaiopoulos
mesh_terms: D020520:Brain Infarction / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D010960:Plasminogen Activators / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D010960:Plasminogen Activators