Author Name(s): Evgeny A. Reshetnikov, Lyubov S. Orlova, Irina V. Batlutskaya, Natalya A. Rudyh, Mikhail I. Churnosov
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To study the association of genetic polymorphisms of coagulation factors with clinical and laboratory indicators in pregnant women with placental insufficiency with fetal growth retardation. Materials and methods: The study group included 250 pregnant women with placental insufficiency with fetal growth retardation (FGR). The control group consisted of 247 women without FGR. The participants were genotyped for four genetic markers of hereditary thrombophilia: fibrinogen (-455G/A FI), prothrombin (20210G/A FII), factor V Leiden (1691G/A FV), proconvertin (10976G/A FVII). Results: In the group of pregnant women with FGR, having genotypes -455GA FI and -455AA FI, a higher level of fibrinogen (4.7 g/l) is observed compared to women with the genotype -455GG FI (4.5 g/l, p=0.04). Conclusion: Thus, the study conducted on the relationship of polymorphic locus -455G/A FI with a higher level of fibrinogen in pregnant women with fetal growth retardation.


Placental Insufficiency, Fetal Growth Retardation, Single Nucleotide Polymorphism, Pregnancy.


Placental insufficiency is a syndrome caused by morphofunctional changes in the placenta, the progression of which develops a fetal growth retardation syndrome, often combined with hypoxia (Bamfo, Odibo, 2011, Zollner et al., 2011; Unanyan et al., 2015). Placental insufficiency (PI) is one of the most common complications of pregnancy (Serov et al., 2011; Diner et al., 2016). Perinatal mortality in women who underwent placental insufficiency is among the full-term newborns 10.3 %, among preterm infants – 49 % (Serov et al., 2011; Diner et al., 2016). In 60% of cases, placental insufficiency leads to the development of FGR, which ranks third in the structure of the causes of perinatal morbidity (Serov et al., 2011). Placental insufficiency has a multifactorial nature (Makacariya, Bicadze, 2006, Serov et al., 2011; Zollner et al., 2011). One of the factors leading to the development of placental insufficiency and FGR is hereditary thrombophilia (Zotz et al., 2008; Facco et al., 2009; Nishizawa et al., 2011; Kosar et al., 2011). But the results of these studies, obtained by different authors, are often contradictory (Camilleri et al, 2004; Infante-Rivard et al., 2005; Dudding et al., 2008; Zotz et al., 2008; Facco et al., 2009; Ivanov et al., 2009; Shanker et al., 2009; Kosar et al., 2011; Nishizawa et al., 2011; Coriu et al., 2014; Livrinova et al., 2015; Reshetnikov et al., 2017).


Our study showed that the genetic variants -455GA FI and -455AA FI are associated with an increased level of fibrinogen in pregnant women with fetal growth retardation. Fibrinogen is a plasma globulin consisting of three pairs of identical polypeptide chains: Aα-, Bβ- and γ. The sequences of the polypeptide chains of fibrinogen are encoded in three different genes located in the long arm of the chromosome 14. Several variants of gene polymorphism have been found, which are in total responsible for fluctuations in the level of fibrinogen in the range of 34-50% (Endler et al., 2003). The -455G/A polymorphism is associated with an increase in the level of fibrinogen (Makacariya, Bicadze, 2006). A high level of fibrinogen in the blood can indicate a high risk of thrombosis (Dyatlova et al., 2015; Makacariya, Bicadze, 2006). Hyperfibrinogenemia is observed in hypercoagulation and in the first stage of DICsyndrome (Dyatlova et al., 2015). Previously, researchers also established a relationship of polymorphism -455 G/A FI with a higher plasma fibrinogen level (Humphries et al., 1987; Makacariya, Bicadze, 2006; Yenicesu et al., 2010). On the contrary, in other works opposite results were obtained (Poursadegh Zonouzi et al., 2013). In our study, were found no significant associations of polymorphic loci 20210G/A FII, 1691G/A FV, 10976G/A FVII with clinico-laboratory parameters in pregnant women with FGR. In other works, contradictory results were also obtained. Thus, several studies have shown the connection of polymorphism 10976G/A FVII with the level of proconvertin in plasma. The presence of the heterozygous variant 10976GA FVII was associated with a decrease in the concentration of factor VII in the blood by about 25%, and in the 10976AA FVII homozygote – with a factor concentration decrease of approximately 50% compared to the carriers of the variant 10976GG FVII (Makacariya et al., 2006, Seremak-Mrozikiewicz et al., 2009). Some researchers have identified associations of polymorphisms of 1691G/A FV and 20210G/A FII with the risk of developing FGR (Martinelli et al., 2001; Dudding, Attia, 2004; Howley et al., 2005); in contrast, (Infante-Rivard et al., 2002).
Thus, the conducted study on the relationship of polymorphic locus -455G/A FI with a higher level of fibrinogen in pregnant women with FGR. The elevated fibrinogen level associated with the carriage of genotypes -455GA FI and -455AA FI can serve as a marker of thrombophilia risk and the development of fetal development retardation syndrome. The obtained results broaden the concept of the role of hereditary thrombophilia in the development of fetal growth retardation and their use in practical obstetrics.

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