title: Association Between Plasminogen Activator Inhibitor-1 Genetic Polymorphisms and Stroke Susceptibility.
abstract: The plasminogen activator inhibitor-1 (PAI-1) is a candidate gene for stroke based on PAI-1's crucial role in fibrinolytic system. However, association studies have yielded conflicting results regarding the association between PAI-1 polymorphisms and stroke susceptibility. To further elucidate the putative association, we performed a systematic review and meta-analysis to provide a complete picture of the loci investigated for association of PAI-1 polymorphism with stroke risk and to derive a precise estimation. PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases were searched until June 2015 to identify eligible studies. Forty data sets from 39 studies with a total of 8336 cases and 14,403 controls were included. The most commonly investigated polymorphism was -675 4G/5G, followed by -844 G/A, 11053 T>G, HindIII C/G, and (CA)n. Overall, our meta-analysis provided evidence for the significant association of PAI-1 4G/5G polymorphism with an increased risk of adult but not pediatric ischemic stroke (adult: 4G/4G vs. 4G/5G + 5G/5G, OR = 1.21, 95 % CI = 1.04-1.42). In the subgroup analysis, significant association was detected in Asians (4G/4G vs. 4G/5G + 5G/5G, OR = 1.45, 95 % CI = 1.14-1.85) but not Caucasians. Moreover, we found that -844 G/A but not 11053 T>G polymorphism was associated with an increased risk of ischemic stroke (-844G/A: A/A vs. G/G: OR = 1.32, 95 % CI = 1.01-1.73). A tendency of PAI-1 4G/5G polymorphism towards a decreased risk of hemorrhagic stroke was observed (4G/4G + 4G/5G vs. 5G/5G, OR = 0.77, 95 % CI = 0.59-1.02, P = 0.066). Future well-designed studies in large well-characterized sample size and presenting results stratified by gender, age, and stroke subtype are warranted.
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zan
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Xie
authors.affiliation: West China Medical School, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Yunke
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. youchao_nswc@163.com.
authors.forename: Chao
authors.initials: C
authors.lastname: You
mesh_terms: D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human
keywords: Hemorrhagic stroke; Ischemic stroke; PAI-1; Polymorphism