Association between plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and risk of Alzheimer's disease, metabolic syndrome, and female infertility

Abstract

Background: Plasminogen activator inhibitor-1 (PAI-1) is considered to be involved in the physiopathological mechanisms of Alzheimer's disease (AD), metabolic syndrome (MetS), and female infertility. Previous studies investigating the association between PAI-1 4G/5G (rs1799889) gene polymorphism and the risk of AD, MetS, and female infertility have reported inconsistent results. The aim of the present study was to investigate possible associations. Methods: Eligible studies were retrieved through PubMed, Medline, EMBASE, CNKI, and WANFANG databases. The odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the associations. Subgroup analyses by ethnicity and mean age, sensitivity analyses, and publication bias were performed. Results: Five studies (four articles) for AD, six studies (six articles) for MetS, and four studies (four articles) for female infertility were included in this meta-analysis. Our results showed no significant associations between the PAI-1 4G/5G polymorphism and the risk of AD and female infertility in five genetic models. For the risk of MetS, the PAI-1 4G/5G (rs1799889) polymorphism may be associated with the risk of MetS (4G vs 5G, OR = 1.31, 95%CI = 1.04–1.64, P = .021), especially in Asians (4G/4G vs 4G/5G+5G/5G, OR = 1.38, 95%CI = 1.01–1.87, P = .041) and patients with mean age > 50 years old (4G/4G vs 4G/5G+5G/5G, OR = 1.36, 95%CI = 1.03–1.78, P = .029). Conclusion: The present meta-analysis suggested that the PAI-1 4G/5G polymorphism might be associated with the risk of MetS, but no evidence was detected for AD and female infertility.

Prothrombotic and Inflammatory Markers in Elderly Patients with Non-Alcoholic Hepatic Liver Disease before and after Weight Loss: A Pilot Study

“…The reduction of PAI-1 and von Willebrand factors (both markers of vascular/endothelial damage) after weight loss strongly suggests an improvement of the endothelial dysfunction, as already reported in a similar paper on metabolic syndrome and inflammation [26].…”

Vascular Dysfunction in Alzheimer’s Disease: Alterations in the Plasma Contact and Fibrinolytic Systems

“…In terms of genetic screenings, a polymorphism in the PAI-1 promoter (4G/4G) that increases PAI-1 transcription has been linked to an increased risk for AD [ 99 ]. However, this was not observed in the Chinese Han population [ 100 ] nor in a recent meta-analysis [ 101 ]. It is important to note that there is one study showing that PAI-1 levels are unchanged in the brains of AD patients, although they show reduced tPA activity [ 82 ].…”

Advances in the study of the correlation between insulin resistance and infertility

“…The prothrombotic state is strongly associated with RSA, and a significant hypercoagulable state may increase thrombotic tendency and make the placenta more susceptible to microthrombosis, which may adversely affect the fetal blood supply and cause adverse pregnancy events such as miscarriage. The mechanism of hyperinsulinemia-induced prothrombotic state formation may be related to the triggering of elevated plasma levels of homocysteine (Hcy) and fibrinogen activator inhibitor 1 (PAI-1) ( 84 , 85 ). Studies ( 86 ) Hcy can affect the normal growth cycle of embryonic cells by influencing DNA methylation, which can lead to apoptosis.…”