Association of Polymorphisms in Plasminogen Activator Inhibitor-1 (PAI-1), Tissue Plasminogen Activator (tPA), and Renin (REN) with Recurrent Pregnancy Loss in Korean Women

Abstract

Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses prior to 20 weeks of gestational age. Various factors, including immune dysfunction, endocrine disorders, coagulation abnormality, and genetic disorders influence RPL. In particular, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), and renin (REN) have important roles in the thrombotic and thrombolytic systems, and abnormal expression of these genes have a reported negative correlation with pregnancy maintenance. Moreover, some polymorphisms of the three genes are related to expression levels and thrombotic disorder. Therefore, we investigated whether polymorphisms of PAI-1, tPA, and REN are linked to RPL. Genotyping of the six polymorphisms (PAI-1 rs11178, rs1050955, tPA rs4646972, rs2020918, REN rs1464816, and rs5707) was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and associations of the polymorphisms with RPL were evaluated by statistical analysis. The polymorphism PAI-1 rs1050955 GA+AA was associated with decreased RPL risk (AOR, 0.528; 95% CI 0.356–0.781; p = 0.001) as was the REN 10795 rs5707 GG genotype (AOR, 0.487; 95% CI 0.301–0.787; p = 0.003). In contrast, the tPA rs4646972 II genotype correlated with increased RPL risk (AOR, 1.606; 95% CI, 1.047–2.463; p = 0.030). This study provides evidence that tPA Alu rs4646972 may contribute to the risk of idiopathic RPL, but PAI-1 12068 rs1050955 and REN 10795 rs5707 are associated with a decreased risk of RPL. Therefore, these alleles may be useful as biomarkers to evaluate the risk of RPL.

Association Study between Mucin 4 (MUC4) Polymorphisms and Idiopathic Recurrent Pregnancy Loss in a Korean Population

“…Moreover, environmental factors such as infection, smoking, alcohol, psychological trauma, and stress may contribute to RPL [ 8 , 9 , 10 ]. However, the cause of RPL is unclear in 30–40% of cases, and recent studies suggest that genetic factors play an important role in the pathogenesis of idiopathic RPL [ 11 , 12 ].…”

Systematic review and meta-analysis of association between plasminogen activator inhibitor-1 4G/5G polymorphism and recurrent pregnancy loss: an update

“…Several research has looked into the potential risk of RPL in patients with PAI-1 4G/5G polymorphism in recent years, but the results have been equivocal or conflicting [ 2 , 8 , 9 , 17 , 22 , 24 , 25 , 38 , 42 ]. This contradiction could be due to issues such as uncorrected multiple hypothesis testing, inadequate statistical power, publication biases, and ethnic inequalities.…”

A strong Association between Plasminogen Activator Inhibitor Type - 1 (-657 4G/5G PAI-1) and the Development of Pre-eclampsia

“…Previously acquired or inherited thrombophilia may be inclined to this abnormal placenta. Additional evidence for an underlying hypercoagulable condition has been evidenced in a wide range of placenta pathological studies in subjects with pre-eclampsia indicative of thrombosis, brin deposition, and villous infarcts [9,10].…”