Faculty of Medicine, Institute of Forensic Medicine, University of Belgrade.
Faculty of Applied Ecology Futura, Metropolitan University, Belgrade, Serbia.
Blood Coagul Fibrinolysis. 2021 Mar 1;32(2):103-107. doi: 10.1097/MBC.0000000000000995.
During normal pregnancy depressed fibrinolytic system is caused by changes in many factors, which could be influenced by different gene polymorphisms. The aim of this study was to investigate the combination of fibrinolysis-related gene polymorphisms in women with idiopathic infertility. We genotype polymorphisms 4G/5G in plasminogen activator inhibitor type 1 (PAI-1), Val34Leu in factor XIII (FXIII) and I/D in angiotensin-converting enzyme (ACE) gene. The patients group consisted of 83 females with idiopathic infertility, while the control group included 121 females with at least one born child. The alleles and genotypes distributions showed no significant differences between analyzed groups. Although higher frequency of PAI-1 5G5G genotype in patients did not reach statistical significance, 5G5G genotype of PAI-1 in combination with ValVal genotype of FXIII leads to higher risk for infertility (P < 0.05). In addition, when we added ACE I/D polymorphism in analysis, the 4G in PAI-1 and D allele in ACE, showed protective effect in combination with FXIII polymorphism (P < 0.05). The finding that combined homozygosity of 5G of PAI-1, commonly associated with greater fibrinolytic activity and bleeding tendency, in combination with Val genotype of FXIII impose a risk for female idiopathic infertility. The protective effect of alleles 4G (PAI-1) and D (ACE) suggest that different combinations of polymorphisms influencing fibrinolysis could lead to better established hemostatic balance and reproductive success. Further analyses, with larger number of samples, as well as assessment of additional biochemical parameters of fibrinolysis, should be performed to clarify the role of gene polymorphisms on fibrinolysis and consequently their influence on reproductive success.
在正常妊娠期间，许多因素会导致纤溶系统受到抑制，这些因素可能受到不同基因多态性的影响。本研究旨在探讨纤维蛋白溶解相关基因多态性在特发性不孕妇女中的组合。我们对纤溶酶原激活物抑制剂 1（PAI-1）的 4G/5G 多态性、凝血因子 XIII 的 Val34Leu（FXIII）多态性和血管紧张素转换酶（ACE）基因的 I/D 多态性进行了基因分型。患者组包括 83 名特发性不孕女性，对照组包括 121 名至少生育过一名子女的女性。分析组之间的等位基因和基因型分布无显著差异。虽然患者 PAI-1 5G5G 基因型的频率较高，但未达到统计学意义，PAI-1 的 5G5G 基因型与 FXIII 的 ValVal 基因型相结合会增加不孕的风险（P<0.05）。此外，当我们在分析中加入 ACE I/D 多态性时，PAI-1 的 4G 和 ACE 的 D 等位基因与 FXIII 多态性相结合，表现出保护作用（P<0.05）。PAI-1 的 5G 常见于纤维蛋白溶解活性增加和出血倾向增加，与 FXIII 的 Val 基因型相结合会增加女性特发性不孕的风险。等位基因 4G（PAI-1）和 D（ACE）的保护作用表明，影响纤溶的多态性的不同组合可能导致更好的止血平衡和生殖成功。应进行进一步的分析，使用更大的样本量，并评估纤溶的其他生化参数，以阐明基因多态性对纤溶的作用及其对生殖成功的影响。
