The significance of genetic polymorphisms of factor V leiden and prothrombin in the preeclamptic polish women

Abstract

Many studies established that gestational hypertension (GH) and preeclampsia (PE) are multifactorial diseases and disturbances in coagulation cascade have etiological significance. Inherited thrombophilias, like polymorphism of factor V (FV) Leiden and prothrombin (PTM) are considered to be involved in the PE development. The aim of this study was to determine the association between FV Leiden and G20210A of PTM gene polymorphism and GH/PE appearance. The study comprised 235 women: GH (n = 126, mean age 27.5 +/- 6.0 years), mild PE (n = 41, mean age 28.3 +/- 5.7 years), and severe PE (n = 68, mean age 28.5 +/- 5.7 years). The control group consisted of 400 healthy pregnant women (mean age 27.5 +/- 4.7 years). All women included in the study were white Caucasian of Polish origin, and were singleton pregnancies. The G1691A polymorphism of FV and G20210A polymorphism of PTM were detected using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) assays. For PTM G20210A polymorphism overrepresentation of heterozygous GA genotype (7.4 vs. 1.2%, P = 0.02) and of A allele (3.7 vs. 0.6%, P = 0.02) in the group of severe PE have been found. For FV G1691A polymorphism the overrepresentation of genotypes containing at least one mutated allele A (GA and AA) in the group of women with mild (9.7 vs. 3.5%, ns) and severe PE (8.8 vs. 3.5%, ns) was observed. Our results suggest the significant influence of G20210A prothrombin polymorphism and possible influence of G1691A factor V polymorphism in the development of severe preeclampsia.

Thrombophilic mutations and susceptibility to preeclapmsia in Western Iran

“…Also, a significantly higher prevalence of FVL mutation and its association with preeclampsia among Finnish [12] and Italian [13] women with preeclampsia have been reported. Seremak-Mrozikiewicz et al [29] in a sample of Polish preeclamptic women observed a significant association between prothrombin G20210A mutation and the development of severe preeclampsia. In another study, Prasmusinto et al [30] examined the frequency of FVL among Germans/Croatia and Indonesian and detected population differences in the association of FVL with increased risk of preeclampsia among Germans/Croatia but not in Indonesian.…”

Association between Thrombophilia Gene Polymorphisms and Preeclampsia: A Meta-Analysis

“…Table 1 and 2 present the results of studies that include cases of preeclampsia (not necessarily defined as severe), and Table 3 and 4 show the studies that include cases identified as severe preeclampsia. In twelve studies [15]–[17], [22], [25], [37]–[40], [48], [49], [52], only severe preeclampsia was defined and in seven[9], [10], [18], [32]–[35], the authors defined both preeclampsia and severe preeclampsia and performed further analysis of the association between the two polymorphisms and severe preeclampsia after analysis for all preeclampsia. In the remaining studies, the authors only defined preeclampsia and didn’t describe the distribution of mild and severe cases.…”

“…In terms of disease definition, the criteria of the American College of Obstetricians and Gynecologists [13] and the National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy [14] were mostly used, in 13 [10], [15]–[26] and 6 [9], [27]–[31] studies, respectively, among which the definitions of preeclampsia and severe preeclampsia varied little. In these studies, preeclampsia was defined as systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg, with the presence of proteinuria by 24-h urinary excretion exceeding 300 mg after 20 weeks of gestation.…”

“…From then on these two genetic polymorphisms were inferred to be associated with PE and many studies have been conducted to explore the relationship between them. Several studies suggested that FVL [7]–[9] and PT 20210 polymorphism [9], [10] were associated with an increased risk of preeclampsia. However, other studies showed inconsistent results.…”

Entropy-based selection for maternal-fetal genotype incompatibility with application to preterm prelabor rupture of membranes

“…For example, it is reported in an earlier twins study that heritability was 17 % for preterm delivery in first pregnancy and 27 % for preterm delivery in any pregnancy [6] and heritability range of 25%–40% was suggested for birthweight and gestational length in another study [7]. Maternal and fetal genes, either individually or in combination, could increase the risk of diseases such as hemolytic disease of the newborn [8], preterm birth [9,10], small for gestational age [11], pre-eclampsia [12-14], and preterm prelabor rupture of membranes (pPROM) [15]. The incompatibility between maternal and fetal genotypes, in which the expression of genes from two generations lead to an opposite effect, plays a vital role and can increase the risk of these diseases.…”