Candidate Genes and Clinical-Laboratory Indices in Pregnant Women Depending on the Development of Preeclampsia

Author Name: Evgenii A. Reshetnikov, Vladimir F. Kulikovskii, Irina V. Batlutskaia, Tatiana I. Iakunchenko, Aleksei V. Polonikov, Mikhail I. Churnosov
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Objectives: The relationship between polymorphic variants of folate metabolism genes with clinical (blood pressure level before and at the end of pregnancy) and clinical and laboratory indicators (proteinuria, fibrinogen, total protein, urea and creatinine in the blood, activated partial thromboplastin time, thrombin time) were studied in pregnant women with preeclampsia. Materials and Methods: The study group included 322 pregnant women diagnosed with preeclampsia and 179 women with normal pregnancy. Polymorphisms of the folate cycle genes (MТHFR +677С>Т (rs1801133), MТHFR +1298 A>С (rs1801131), MТRR +66 A>G (rs1801394), MТR +2756 A>G (rs1805087)) were studied by real-time polymerase chain reaction (PCR) of DNA synthesis (Real-time-PCR). Results: Polymorphic markers +2756 AA MТR and +1298 AС, +1298СС MТHFR are associated with an increased level of diastolic and systolic blood pressure, respectively, in women with pre-eclampsia prior to pregnancy. The genotypes +677ST and + 677TT MTHFR are associated with an increased level of proteinuria, and the genetic variants of +2756 AA MTR and +66GG MTRR are associated with a lower protein content in the blood and a high proteinuria level in pregnant women with preeclampsia. Conclusions: Thus, as a result of this study, significant associations of genetic polymorphisms MТHFR +677С>Т, MТHFR +1298 A>С, MТR +2756 A>G, MТRR +66 A>G with indices of blood pressure, protein content in the blood, proteinuria level in pregnant women with preeclampsia were determined.


Preeclampsia is a multisystem pathological condition that occurs in the second half of pregnancy (after the 20th week) characterized by hypertension in combination with proteinuria, often with edema and multiple organ dysfunction (Williams et al, 2011, Sidorova, 2016). The frequency of PE is 8-20% among all pregnant women (Suhih, Murashko, 2010). During the last decade, preeclampsia is one of the main factors of perinatal morbidity in the world and stably ranks 3rd-4th in the structure of the causes of maternal morbidity and mortality (Ajlamazyan, Mozgovaya, 2010, Sidorova, 2016).

Analysis of modern literature indicates that PE is a multifactorial disease. Genetic component of PE development can account for up to 50% of all risk factors (Baranov, 2009; Reshetnikov et al., 2017).

An important role in the etiology and pathogenesis of preeclampsia belongs to the candidate genes for folate metabolism (Vorozhishcheva, 2014; Zhou et al., 2016). Mutations in the genes of folate metabolism, which lead to a decrease in the activity of methyltetrahydrofolate reductase enzymes and methionine synthase reductase, lead to an excessive accumulation of homocysteine in the blood and, as a result, disruption of methylation processes in cells (Vorozhishcheva, 2014). Deficiency of folic acid causes the formation of hypertension in pregnant women, the development of total angiopathy, microthrombosis, increased insulin resistance. It should be noted that the role of candidate genes for folate metabolism in the formation of PE has been actively studied, but these studies often give conflicting results in different populations of the world (Obolenska et al., 2011; Pavlova et al., 2011; Williams et al., 2011; Valenzuela et al., 2012; Reilly et al., 2014; Vorozhishcheva, 2014;).


The data obtained as a result of the research broaden the understanding of the mechanisms of preeclampsia development, and also allows predicting the nature of the clinical course of the disease, which will ensure optimization of the treatment and diagnostic process for each patient. The polymorphisms MТR +2756 A>G, MТHFR +1298 A>С, MТHFR +677С>Т, MТRR +66 A>G can be used to predict blood pressure levels, proteinuria levels, and protein content in pregnant women with preeclampsia. MТHFR +677С>Т (rs1801133), MТHFR +1298 A>С (rs1801131), MТRR +66 A>G (rs1801394), MТR +2756 A>G (rs1805087))


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