Association of PAI-1 rs1799889 Polymorphism with Susceptibility to Ischemic Stroke: a Huge Meta-Analysis based on 44 Studies

Abstract

Background: the PAI-1 rs1799889 polymorphism has been reported to be associated with susceptibility to ischemic stroke. However, the results of previous studies have been inconsistent or controversial. Hence, we performed a systematic review and meta-analysis to evaluate the association of PAI-1 rs1799889 polymorphism with ischemic stroke risk. Methods: A comprehensive literature search was performed on PubMed, Web of Science, Scopus, SciELO, CNKI, and CBD databases up to November 05, 2019. Pooled odds ratio (OR) with 95% confidence interval (CI) were used to access the strength of this association in fixed- or random-effects model. Results: A total of 44 case-control studies with 8,620 cases and 10,260 controls were selected. Pooled data showed a significant association between PAI-1 rs1799889 polymorphism and ischemic stroke risk in the overall populations (GG vs. AA: OR = 0.791, 95% CI 0.633–0.988, p = 0.039; GA vs. AA: OR = 0.807, 95% CI 0.683–0.953, p = 0.012; and GG+GA vs. AA: OR = 0.795, 95% CI 0.637–0.993, p = 0.043). Subgroup analysis by ethnicity revealed a significant association in Asian and Mixed populations, but not in Caucasians. Moreover, stratified analysis by country of origin revealed an increased risk of ischemic stroke in Chinese populations, but not among Dutch (Netherlands) and Swedish. Conclusions: This meta-analysis result suggested that PAI-1 rs1799889 polymorphism was associated with an increased risk of ischemic stroke, especially in Asian and Mixed populations.

Association of PON1, LEP and LEPR Polymorphisms with Susceptibility to Breast Cancer: A Meta-Analysis

“…Finally, 39 case-control studies including 7 studies with 2005 cases and 2,748 controls were on PON1 rs662, 6 studies with 2,031 cases and 1,973 controls on PON1 rs854560, 12 studies with 3,444 cases and 3,583 controls on LEP rs7799039, and determined by Z-test, in which P<0.05 was considered statistically significant. The associations was evaluated under all five genetic models, i.e., allele (B vs. A), homozygote (BB vs. AA), heterozygote (BA vs. AA), dominant (BB+BA vs. AA), and the recessive (BB vs. BA+AA), in which ''B'' presents mutant and ''A'' wild allele (Jafari-Nedooshan et al, 2019;Jafari et al, 2020). Between-study heterogeneity was estimated using a Cochran-based Q statistical test, with P-values less than 0.1 indicated the absence of indicated heterogeneity among studies.…”

Association of plasminogen activator inhibitor-1 4G5G Polymorphism with risk of diabetic nephropathy and retinopathy: a systematic review and meta-analysis

“…The human PAI-1, a serine protease inhibitor (also known as Serpin E1) is located on chromosome 7q21.3-q22, consists of 9 exons and with a length of 12.2 kb [29]. The PAI-1 promoter contains a common − 675 4G5G polymorphism that may affect both basal and inducible PAI-1 expression [30,31]. The progress in the knowledge about the role of PAI-1 gene in up regulation of hyperinsulinemia and hyperglycemia have led to several studies have tested a potential association of the PAI-1 4G5G polymorphism with development of DR and DN in diabetic patients [32], but the results were conflict.…”

Ethnic Difference of Thrombogenicity in Patients with Cardiovascular Disease: a Pandora Box to Explain Prognostic Differences

“…PAI-1 rs1799889 4G/5G polymorphism (4G vs. 5G) has been associated with an increased risk of DVT, MI and ischemic stroke. 54) 55) 56) …”

“…The significant linkage of PAI-1 rs1799889 polymorphism (4G vs. 5G) to the risks of DVT, CAD and ischemic stroke was more prominent in the Asian population. 55) 56) Limited studies have also identified lower levels of circulating protein C and protein S, and endogenous anticoagulants in African Americans. 59) 60) …”