Genetic association studies of ACE and PAI-1 genes in women with recurrent pregnancy loss

Abstract

SummaryA fine balance between coagulation and fibrinolysis is critical in early pregnancy. Plasminogen activator inhibitor-1 (PAI-1) and angiotensin converting enzyme (ACE) are involved in the fibrinolytic process, and several studies have reported the association between their gene polymorphisms and recurrent pregnancy loss (RPL). This study was conducted to investigate the association between PAI-1 and ACE polymorphisms and idiopathic RPL, using meta-analyses. A systematic review of the published literature from the MEDLINE and EMBASE databases before April 2012 was conducted. Of 209 potentially relevant studies, 22 case-control studies comprising a total of 2,820 RPL patients and 3,009 controls were included. Among these studies were 11 reports of PAI-1 4G/5G and 11 of ACE I/D polymorphisms in patients with RPL. A significant association was found withthe ACE I/D polymorphism [summary odds ratio 1.29 (95% confidence interval 1.02-1.62)] in studies including more than two recurrent abortions. Subgroup analysis did not show significant associations with RPL in Caucasian and non-Caucasian patients. Meta-analyses of PAI-1 4G/5G polymorphism were not found associations with RPL in studies including more than two or three recurrent abortions, and in studies of Caucasian and non-Caucasian patients. In conclusion, meta-analyses showed a significant association between the ACE I/D polymorphism and idiopathic RPL. High clinical heterogeneity existed among studies of PAI-1 4G/5G, and the aggregated data failed to confer higher susceptibility to idiopathic RPL. More well-designed studies with different ethnic populations are required for future integration.

Association between Plasminogen Activator Inhibitor‐1 Gene Polymorphisms and Recurrent Pregnancy Loss: A Systematic Review and Meta‐Analysis

“…In a previous study, Su et al 36 did not observe any association between the PAI-1-675G/A polymorphism and RPL based on 1545 cases and 960 controls. Moreover, Parveen et al 23 reported a null association between the -675G/A polymorphism and RPL risk based on 868 cases and 627 controls, which was not consistent with the present results of our meta-analysis.…”

Thrombotic and Hemostatic Aspects of Assisted Conception

“…Heritable hypofi brinolysis, mediated by 4G/4G homozygosity for the PAI-1 gene, may be associated with late placenta-mediated pregnancy complications, postulated to be through thrombotic induction of placental insuffi ciency [ 69 ]. A meta-analysis of the PAI-1 4G/5G polymorphism showed no associations with two or three pregnancy losses [ 70 ].…”

Toward optimal set of single nucleotide polymorphism investigation before IVF

“…This multifunctional protein plays a key role in processes such as regulation of blood pressure, maintain a balance of electrolytes, platelet activation and aggregation, fibrinolysis. ACE protein functionality and features of its expression, associated with the presence of Alu-sequences in the intron, are devoted to a great number of publications [55,56,[60][61][62]. Virtually all studies agree that the presence of variant D (Del), lack of Alu-sequences in the intron of the ACE gene, is associated with atherosclerotic, cardiovascular disorders and the risk of pregnancy violation [29,61,62].…”

“…ACE protein functionality and features of its expression, associated with the presence of Alu-sequences in the intron, are devoted to a great number of publications [55,56,[60][61][62]. Virtually all studies agree that the presence of variant D (Del), lack of Alu-sequences in the intron of the ACE gene, is associated with atherosclerotic, cardiovascular disorders and the risk of pregnancy violation [29,61,62]. At the molecular level, Alu insertion reduces the gene expression level that is displayed as s decrease in the level of ACE protein in the blood and more precise regulation of blood pressure without pronounced spikes as a consequence.…”