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

Abstract

Aim As angiogenesis is an essential step for chorionic villi formation. Vascular endothelial growth factor (VEGF) is essential for endothelial cell proliferation. Endothelial nitric oxide synthase (eNOS) is a powerful playmaker in hypoxia‐induced angiogenesis. Thrombin‐activatable fibrinolysis inhibitor (TAFI) regulates both fibrinolysis and inflammation. Genetic alterations of these factors may lead to recurrent spontaneous abortion (RSA). We aimed to investigate the combined genetic variants of VEGF G‐1154A and two eNOS genetic variants: T‐786C promoter region and intron 4 variable number of tandom repeats in addition to TAFI C‐1040T among RSA patients. Methods The study included 50 patients with RSA and 50 healthy controls. Polymerase chain reaction and restriction fragment length polymorphism were used for genotyping. Results Both genetic alterations of eNOS confirmed at least a sixfold increase of RSA risk. Interestingly, they were associated with TAFI C‐1040Tgenetic variant in 21 patients, eight of them had both studied eNOS genetic alterations and TAFI C‐1040Tgenetic variant, while each eNOS genetic variant associated with TAFI C‐1040Tconfirmed an almost one and half fold increase risk of RSA. Conclusion These findings highlighted the role of eNOS and nitric oxide metabolism in RSA and opened the gate to investigate the interaction of vasoconstrictive and fibrinolytic inhibitor systems.

Relationship Between Polymorphism of Thrombin-Activatable Fibrinolysis Inhibitor Gene +1040C/T and a Cohort of Chinese Women With Recurrent Spontaneous Abortion

“…The frequency of the C allele was lower among RSA cases than controls (0.78 vs 0.84) and the C/C genotype frequency was also lower among women with RSA (57.66% vs 68.93%), but the differences in allele and genotype distributions were not significant (both P > 0.05), in accordance with other studies in different populations. 14 , 17- 20 The overall prevalence of the CC genotype in the current study population was 62.5%, including 57.66% in the RSA group and 68.93% in the control group.…”

“…22,23 TAFI þ1040C/T is a commonly studied polymorphic variant for RSA. 14,[17][18][19][20] Nevertheless, the protective role of the C allele of this polymorphism is controversial. The frequency of the C allele was also related to ethnicity among women with RSA, with incidences of 59.3% in 86 Italian women, 14 59.33% in 59 Serbian women, 17 73% in 50 Egyptian women, 18,19 and 15.6% in 426 Chinese women.…”

“… 14 , 17- 20 Nevertheless, the protective role of the C allele of this polymorphism is controversial. The frequency of the C allele was also related to ethnicity among women with RSA, with incidences of 59.3% in 86 Italian women, 14 59.33% in 59 Serbian women, 17 73% in 50 Egyptian women, 18 , 19 and 15.6% in 426 Chinese women. 20 Although all the frequencies of the C allele mentioned above were lower in RSA patients compared with controls, the differences were not significant.…”

“…17 Although the frequency of the T allele was higher among Egyptian patients with RSA and the frequency of the C allele was higher in controls, the difference was not significant, suggesting that TAFI þ1040C/T was not a molecular predictive factor for RSA. 18,19 In addition, the TAFI þ1040C/T polymorphism was not related to RSA in Chinese Han women. 20 These studies suggest that the þ1040 SNP in the coding region of the TAFI gene in relation to RSA might differ among ethnic groups.…”

Association of IL-1β, IL-6, TNF-α, and TGFβ1 Gene Polymorphisms with Recurrent Spontaneous Abortion in Polycystic Ovary Syndrome

“…Cytokines are important for normal pregnancy development, and any abnormality in quantity or locality of expression may affect trophoblast-endometrial interaction leading to pregnancy complications including RSA [33,34]. Although the contribution of a broad spectrum of SNPs in cytokinecoding genes to RSA has been extensively investigated, their role remains unclear [28,31,[34][35][36]. We examined the possible associations of IL-1β, IL-6, TNF-α, and TGFβ1 gene polymorphisms with RSA Saudi patients with or without PCOS.…”