Thrombin-Activatable Fibrinolysis Inhibitor Gene Polymorphism (TAFI1040C/T) in Women With Recurrent Spontaneous Abortion

Abstract

Recurrent spontaneous abortion (RSA) is defined as 3 or more consecutive pregnancy failures. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a plasma zymogen that regulates both fibrinolysis and inflammation. The TAFI 1040C/T polymorphism could alter the circulating levels of TAFI with a reduced capacity to remove the fibrin clots from the circulation; therefore, it could be considered a molecular risk factor for RSA. The TAFI 1040C/T polymorphism was studied in 50 patients with RSA by polymerase chain reaction-restriction fragment length polymorphism technique and compared to 50 age- and gender-matched healthy volunteers as a control group to verify its possible association with RSA. In case group, the wild genotype (C/C) and heterozygous genotype (C/T) did not reduce the risk of RSA (odds ratio: 0.368 and 0.767, respectively), even when compared to the number of RSA ( P = .71). A higher frequency of C allele in the control group and a higher frequency of T allele in the case group were observed but with no statistical significance. In conclusion, our study revealed that TAFI 1040C/T could not be considered a molecular predictive factor for RSA in Egyptians.

The prevalence of combined vascular endothelial growth factor, endothelial nitric oxide synthase and thrombin‐activatable fibrinolysis inhibitor genetic polymorphisms among Egyptian patients with recurrent spontaneous abortion

“…The aim of the current work was to investigate the possible impact of combined genetic variants of VEGF G‐1154A gene and two eNOS genes: T‐786C promoter region and intron 4 VNTR in addition to TAFI C‐1040 T among Egyptian patients with RSA, which could be a novel highlight on the genetic interaction of the factors affecting angiogenesis, vasoconstrictive and fibrinolytic system, hoping for better understanding of such interactions and to find targeted therapies that can optimize plasma levels of such factors to ameliorate the incidence of RSA. All the studied genetic variants were significantly higher among the RSA patient group than the controls, except for TAFI C‐1040Tgenetic variant …”

“…After publishing our previous results which concluded that; TAFI 1040C/T could not be considered as a molecular predictive factor for RSA in Egyptians, we could not find any published research that investigated the role of TAFI whether on the molecular or antigen level in pregnancy nor RSA until the time of preparation of the current work. Both eNOS T‐786C and 27bp VNTR of intron 4 were associated in 10 patients who were negative for other studied genes, similarly Almawi et al , found genetic association study replicated a significant association for eNOS variants and haplotypes with RSA.…”

“…Formation of new blood vessels (angiogenesis) is the most crucial step in the formation of chorionic villi, on which the early fetal life is dependent. Any factor affecting such an important step or affecting the activity of the lining endothelium may lead to its obstruction by blood clots, and if there is an additional lower capability to remove such clots, this may lead to early fetal loss …”

“…Thrombin‐activatable fibrinolysis inhibitor (TAFI), or procarboxypeptidase U, is a circulating human plasma zymogen that is considered a novel link of coagulation to fibrinolysis, the later regulates early human trophoblastic invasion. It also has a role in the process of inflammation . TAFI levels in the maternal circulation were reported to be gradually increased during pregnancy with a peak in the last trimester, particularly in complicated pregnancy, and then to return to normal levels after the first day postpartum.…”

“…Any factor affecting such an important step or affecting the activity of the lining endothelium may lead to its obstruction by blood clots, and if there is an additional lower capability to remove such clots, this may lead to early fetal loss. 7 Pregnancy is categorized as one of the hypercoagulable states. Cytokines, angiogenic mediators, hormones and a delicate balance between procoagulant and anticoagulant factors are the chief mediators that play crucial roles in all stages of reproduction.…”