M385T polymorphism in the factor V gene, but not Leiden mutation, is associated with placental abruption in Finnish women
Introduction
Dahlback et al. [1] assigned the factor V gene to chromosome region 1q23. Activated Factor V (Factor Va) is an essential cofactor for the factor Xa-catalyzed activation of prothrombin to the clotting enzyme thrombin [2]. Activated protein C (APC) is a naturally occurring anticoagulant which selectively degrades coagulation factors Va and VIIIa [3]. The factor V Leiden mutation, a common point mutation in the factor V gene, encoding substitution of arginine for glutamate at position 506 of the factor V molecule, has been reported to be the site where activated protein C cleaves factor Va [4]. The factor V Leiden mutation and R485K polymorphism in the factor V gene (the less frequent A allele (K485)) have been reported to be a significant risk factor for thrombophilia [5], [6], [7], [8].
In obstetrics, the prevailing evidence suggests that the risk of placental abruption is increased two- to sixfold in women carrying the factor V Leiden mutation [9], [10]. The central mechanism is probably endothelial cell injury and dysfunction resulting from fibrin deposition and the formation of microthrombi [11]. We designed a controlled study to investigate the possible association between not only the Leiden mutation, but also the M385T and R485K polymorphisms of the factor V gene and placental abruption in Finnish women. We further analysed the haplotype structure in the critical area covering a region in the proximity of the Leiden mutation. The Finnish population is considered to be a genetic isolate and thus ideal for genetic association studies [12].
Section snippets
Materials and methods
Written approval for the study was obtained from the Ethics Committee of Kuopio University Hospital, and the Institutional Review Board approved the protocol. All subjects gave written informed consent, which was documented.
Information was collected retrospectively in connection with 117 pregnancies of parous women who had had placental abruption and 115 parous control women with no history of placental abruption who delivered at Kuopio University Hospital between January 1994 and December
Results
Selected clinical characteristics of affected women and controls are shown in Table 1. Of the 116 women with placental abruption, 45 were nulliparas, whereas all the (selected) controls had had two or more uncomplicated deliveries, in order to reduce the stratification bias that would have resulted from the fact that primiparous women may experience placental abruption in subsequent pregnancies. In cases of recurrent placental abruption (N=8), only the first incident was used for comparison.
Discussion
The genetic background behind placental abruption is supported by the observed high recurrence rate [14], [15] and genetic associations found between the disease and nitric oxide synthase polymorphisms, Leiden and 5,10-methylenetetrahydrofolate reductase gene mutations [16], [17], [18]. This genetic component is likely to be multifactorial in nature and furthermore, environmental factors probably modify the disease risk individually. In this study, the candidate gene was selected on the basis
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Abruptio placentae risk and genetic variations in mitochondrial biogenesis and oxidative phosphorylation: replication of a candidate gene association study
2018, American Journal of Obstetrics and GynecologyGenetic variations and risk of placental abruption: A genome-wide association study and meta-analysis of genome-wide association studies
2018, PlacentaCitation Excerpt :However, most PA cases do not exhibit these known risk factors [13]. PA tends to aggregate in first degree relatives of women with PA [14,15], suggesting a role for genetic predisposition [16–18]. Accumulating evidence from GWAS and candidate gene studies also suggest that there are underlying genetic risk factors in the pathogenesis of PA [19–23].
Inherited Thrombophilias and Adverse Pregnancy Outcomes. A Review of Screening Patterns and Recommendations
2014, Obstetrics and Gynecology Clinics of North AmericaCitation Excerpt :No significant association exists between FVL G1691A and preeclampsia or small gestational age.15,16 Associations between placental abruption and FVL G1691A are also lacking.17–19 However, a more recent MFM network case control study, although confirming a lack of association with placental abruption, did find an increase in fetal hypoxia-inducing factors in the placentas of mothers with FVL G1691A compared with age-matched controls.20
Factor v Leiden mutation and pregnancy-related complications
2010, American Journal of Obstetrics and GynecologyCitation Excerpt :However, our results did not support the assumption that FVL carriership raises the relative risk of these complications, and it is more important to consider the absolute risks when assessing such rare events. Two prospective studies failed to detect any association between FVL carriership and placental abruption,10,19 as did 2 of the 3 largest retrospective studies.26-28 The largest case-control study found a significantly elevated risk for fetal loss after 22 gestational weeks29 but the largest cohort study did not.30
Inherited and acquired thrombophilias and adverse pregnancy outcomes
2016, Recurrent Pregnancy Loss: Evidence-Based Evaluation, Diagnosis and Treatment