Maternal and Fetal Variants of Genetic Thrombophilias and the Risk of Preeclampsia

Vefring, Hege K.; Lie, Rolv Terje; Ødegård, Rønnaug; Mansoor, M. A.; Nilsen, Stein Tore

doi:10.1097/01.ede.0000112217.33111.23

Cited by 34 publications

(29 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] Our findings in a large white population provide a clear demonstration of the strong association of severe PE with thrombophilia. Diagnosis of PE and assessment of its severity were in strict accordance with the American College of Obstetricians and Gynecologists criteria.…”

Section: Discussionmentioning

confidence: 82%

“…25,31 Pooling mild and severe PE, gestational hypertension, and chronic hypertension is likely to result in inaccurate determination of the exact impact of thrombophilic defects and perhaps a selection bias toward healthier subjects. Our study clearly indicates that only severe PE is associated with a very high prevalence of thrombophilia, in which the prevalence of inherited and acquired thrombophilia in mild PE is similar to that observed in the control group.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the limited size of studies of the association of thrombophilia with PE reduces their statistical significance and may result in its overestimation or underestimation. 15,17,23,24,27,31,32 The size of our sample is one of the strengths of our study. Even so, it was insufficient to detect significant differences in the prevalence of inherited deficiency of protein C, protein S, and antithrombin III, all rather infrequent.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Thrombophilia Is Significantly Associated With Severe Preeclampsia

Mello

Parretti²,

Marozio³

et al. 2005

Hypertension

140

View full text Add to dashboard Cite

Abstract-The role of thrombophilia in the pathogenesis of preeclampsia is controversial. The aim of this case-controlled study was to determine whether thrombophilia increases the risk of preeclampsia or interferes with its clinical course. A total of 808 white patients who developed preeclampsia (cases) and 808 women with previous uneventful pregnancies (controls) matched for age and parity were evaluated for inherited and acquired thrombophilia (factor V Leiden; factor II G20210A; methylenetetrahydrofolate reductase C677T; protein S, protein C, and antithrombin III deficiency; anticardiolipin antibodies; lupus anticoagulant; and hyperhomocysteinemia). Odds ratios (ORs) with 95% confidence intervals (CIs) for risk of being carriers of thrombophilia in cases compared with controls and for risk of maternal life-threatening complications and adverse perinatal outcomes in preeclamptic patients with or without thrombophilia were calculated. Women with severe preeclampsia (406 cases) had a higher risk (OR, 4.9; 95% CI, 3.5 to 6.9) of being carriers of either an inherited or acquired thrombophilic factor, except for protein S, protein C, and antithrombin deficiency. In women with mild preeclampsia (402 cases), only prothrombin and homozygous methylenetetrahydrofolate reductase gene mutations were significantly more prevalent than in the controls. Thrombophilic patients with severe preeclampsia are at increased risk of acute renal failure (OR, 1.8; 95% CI, 1.5 to 2.2), disseminated intravascular coagulation (OR, 2.7; 95% CI, 1.1 to 6.4), abruptio placentae (OR, 2.6; 95% CI, 1.2 to 6.0) and perinatal mortality (OR, 1.7; 95% CI, 1.5 to 2.2) compared with nonthrombophilic preeclamptic patients. Our study demonstrates a significant association between maternal thrombophilia and severe preeclampsia in white women. Thrombophilia also augments the risk of life-threatening maternal complications and adverse perinatal outcomes in preeclamptic patients.

show abstract

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Thrombophilia Is Significantly Associated With Severe Preeclampsia

Mello

Parretti²,

Marozio³

et al. 2005

Hypertension

140

View full text Add to dashboard Cite

show abstract

“…A wide range of genotyping techniques have been described over the years, including gel-based restriction fragment length polymorphism (RFLP) [11,12], "closed tubes" assays such as the 5' fluorogenic nuclease assay (TaqMan assay), single-base extension (minisequencing), Pyrosequencing TM , and amplification refractory mutation system (ARMS) [12]. Some genotyping techniques combine real-time PCR with continuous fluorescence monitoring during amplification; an example is the LightCycler instrument, which uses fluorescence resonance energy transfer (FRET) and real-time PCR.…”

Section: Introductionmentioning

confidence: 99%

Rapid Genotyping of the Human Renin (REN) Gene by the LightCycler® Instrument: Identification of Unexpected Nucleotide Substitutions within the Selected Hybridization Probe Area

et al. 2010

Self Cite

View full text Add to dashboard Cite

Abstract. Preeclampsia is a serious disorder affecting nearly 3% of all pregnancies in the Western world. It is associated with hypertension and proteinuria, and several lines of evidence suggest that the renin-angiotensin system (RAS) may be involved in the development of hypertension at different stages of a preeclamptic pregnancy. In this study, we developed rapid genotyping assays on the LightCycler instrument to allow the detection of genetic variants in the renin gene (REN) that may predispose to preeclampsia. The method is based on real-time PCR and allele-specific hybridization probes, followed by fluorescent melting curve analysis to expose a change in melting temperature (Tm). Ninety-two mother-father-child triads (n = 276) from preeclamptic pregnancies were genotyped for three haplotype-tagging single nucleotide polymorphisms (htSNPs) in REN. All three htSNPs (rs5705, rs1464816 and rs3795575) were successfully genotyped. Furthermore, two unexpected nucleotide substitutions (rs11571084 and rs61757041) were identified within the selected hybridization probe area of rs1464816 and rs3795575 due to aberrant melting peaks. In conclusion, genotyping on the LightCycler instrument proved to be rapid and highly reproducible. The ability to uncover additional nucleotide substitutions is particularly important in that it allows the identification of potentially etiological variants that might otherwise be overlooked by other genotyping methods.

show abstract

“…Several studies have addressed the role of fetal inherited thrombophilias in pre-eclampsia, only three of them have included a small number of HELLP pregnancies (Table 5) (19,23,28,(33)(34)(35)(36)(37)(38). On the whole, there was no evidence for a strong association.…”

Section: Discussionmentioning

confidence: 99%

Maternal Factor V Leiden Mutation Is Associated With HELLP Syndrome in Caucasian Women

Muetze

Leeners

Ortlepp

et al. 2008

Obstetrical &Amp; Gynecological Survey

View full text Add to dashboard Cite

Objective. There is growing evidence that hypertensive pregnancy complications and other adverse pregnancy outcomes are associated with the presence of inherited or acquired thrombophilias. As hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome is one of the most severe forms of pre-eclampsia we aimed to assess the prevalence of the factor V Leiden, the prothrombin 20210G >A mutation and the methylenetetrahydrofolate reductase (MTHFR) 677C >T polymorphism in women with HELLP syndrome and in their fetuses from the same index pregnancy. Design. The study was performed retrospectively in a case-control design. Sample. Seventy-one mother-child pairs with HELLP syndrome and 79 control mother-child pairs with uncomplicated pregnancies were included in the study. Methods. Genotyping of the three thrombophilic mutations was performed using the LightCycler technology. The chi-squared test was used for statistical analysis. Main outcome measures were maternal and fetal genotypes and their correlation with clinical parameters. Results. Maternal heterozygosity for factor V Leiden was significantly more prevalent in the HELLP group than in controls (OR 4.45, 95% CI 1.31-15.31). No significant association was observed for maternal prothrombin mutation or MTHFR polymorphism (p=0.894, p=0.189, respectively). The fetal genotype was not associated with HELLP syndrome for any of the three mutations investigated. Analysis of gene-gene interactions and genotype-phenotype correlation with respect to clinical parameters and perinatal outcome revealed no further differences. Conclusions. Our study confirms that women heterozygous for factor V Leiden have an increased risk of developing HELLP syndrome, while the most frequent mutations of the prothrombin and MTHFR gene do not play a major role in the pathogenesis of HELLP syndrome. AbstractObjective: There is growing evidence that hypertensive pregnancy complications and other adverse pregnancy outcomes are associated with the presence of inherited or acquired thrombophilias. As HELLP syndrome is one of the most severe forms of pre-eclampsia we aimed to assess the prevalence of the factor V Leiden, the prothrombin 20210G>A mutation and the MTHFR 677C>T polymorphism in women with HELLP syndrome and in their fetuses from the same index pregnancy. Design:The study was performed retrospectively in a cas-control design. Sample: 71 motherchild pairs with HELLP syndrome and 79 control mother-child pairs with uncomplicated pregnancies were included in the study. Methods: Genotyping of the three thrombophilic mutations was performed using the LightCycler technology. The chi-squared test was used for statistical analysis.

show abstract

Maternal and Fetal Variants of Genetic Thrombophilias and the Risk of Preeclampsia

Cited by 34 publications

References 26 publications

Thrombophilia Is Significantly Associated With Severe Preeclampsia

Thrombophilia Is Significantly Associated With Severe Preeclampsia

Rapid Genotyping of the Human Renin (REN) Gene by the LightCycler® Instrument: Identification of Unexpected Nucleotide Substitutions within the Selected Hybridization Probe Area

Maternal Factor V Leiden Mutation Is Associated With HELLP Syndrome in Caucasian Women

Contact Info

Product

Resources

About