An update meta analysis of the Relationship between the SNP rs1799889 in PAI-1 and risk of RPL

Abstract

Abstract Objective To investigate the association between recurrent spontaneous abortion and plasma plasminogen activator inhibitor-1 (plasminogen activator inhibitor-1, PAI-1) gene promoter insertion and deletion polymorphism (4G / 5G). Methods Electronic database was used to search the articles related to PAI-1 4G/5G polymorphism and recurrent abortion from the establishment of the database to September 2023. Allele model, dominant model, recessive model, co-dominant model (including homozygous model and heterozygous model) and overdominant model were used to study the relationship between 4G/5G polymorphism of PAI-1 gene and recurrent abortion. Odds ratio (OR) and 95% confidence interval were used to evaluate the intensity of the association, and then subgroup analysis was carried out according to race, number of miscarriages and continuity of abortions. Galbraith diagram was used to find the source of heterogeneity, and Begger test was used to evaluate the publication bias of all studies. Results A total of 39 studies were included in this paper. In the overall analysis, only the gene polymorphism in the overdominant model decreased the risk of recurrent abortion (OR = 0.82,95%CI:0.70–0.98), while in other gene models, it increased the risk of recurrent abortion in varying degrees (OR values ranged from 1.50 to 2.11). In the ethnic subgroup, there was no correlation between the two in the yellow race under the overdominance model (OR = 0.91,95%CI:0.70–1.19), but there was a significant correlation in other models (the OR value was between 1.161.67). In Caucasians, the risk of recurrent abortion was reduced under the overdominant model (OR = 0.79,95%CI:0.71–0.89), but increased in different degrees in other models (OR value between 1.32 and 2.23). In the subgroup of times of abortion, the subgroup with more than 3 abortions was only correlated with allele model (OR = 1.24,95%CI:1.00-1.54), dominant model (OR = 1.49,95%CI:1.17–1.90) and heterozygote model (OR = 1.59,95%CI:1.14–2.23). In ≥ 2 subgroups, the gene polymorphism decreased the risk of recurrent abortion under overdominant model (OR = 0.88,95%CI:0.79–0.98), while in other models, the gene polymorphism was positively correlated with the risk of recurrent abortion (OR value was between 1.35 and 1.87). In the continuous abortion subgroup, there was no correlation between the two in the continuous abortion group only under the overdominant model (OR = 0.93,95%CI:0.77–1.13), but there was a significant correlation with recurrent abortion in other gene models (OR values between 1.32 and 1.77). Discontinuous abortion group significantly reduced the risk of recurrent abortion under overdominant models (OR = 0.74,95%CI:0.64–0.85), while other models increased the risk of recurrent abortion (OR values between 1.40 and 2.32). Conclusion This Meta analysis study shows that the 4G/5G polymorphism of PAI-1 gene is associated with recurrent abortion, and 4G allele increases the risk of recurrent abortion. In clinical work, for women of childbearing age who have a history of abortion and carry 4G alleles, relevant strategies should be taken to prevent the occurrence of recurrent abortion.