Changes of Resistance to Activated Protein C in the Course of Pregnancy and Prevalence of Factor V Mutation

Mimuro, Shigeko; Lahoud, Robert; Beutler, Lucinda; Trudinger, Brian J.

doi:10.1097/00006254-199901000-00003

Cited by 12 publications

(17 citation statements)

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“…We have not confirmed the recent observations of Grandone et al [13] who, in an Italian population, reported a strong independent association between the prothrombin G20210A gene mutation and pre-eclampsia. In addition, our findings are not in keeping with previous reports of associations between other inherited thrombophilias and pre-eclampsia [1][2][3][4]16]. These differences may be explained, in part at least, by the different ethnic background of the subjects, the different methods of subject ascertainment and the increased size and power of our study.…”

Section: Discussioncontrasting

confidence: 98%

“…The aetiology of preeclampsia is still poorly understood. Several recent reports have described associations between the inherited thrombophilias, including the common mutation (C677T) of methylenetetrahydrofolate reductase (MTHFR), the factor V Leiden mutation and protein C deficiency, and pre-eclampsia [1][2][3][4][5][6]. It has been postulated that excessive microthrombi within the uteroplacental circulation may explain these associations.…”

Section: Introductionmentioning

confidence: 99%

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Prothrombin G20210A Mutation: Is It Associated with Pre-Eclampsia?

Higgins¹,

Kaiser²,

Moses³

et al. 2000

Gynecol Obstet Invest

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Objective: A strong independent association between the prothrombin G20210A gene mutation and pre-eclampsia has been reported in an Italian population. This result was not confirmed in a subsequent study in a Dutch population. The objective of this study was to further test the hypothesis that the prothrombin G20210A mutation is associated with pre-eclampsia/eclampsia. Methods: Seventeen eclamptics and 67 pre-eclamptics were recruited from 34 multicase Australian/New Zealand families. An additional 105 unrelated pre-eclamptic/eclamptic women and 119 parous women were recruited as controls. Results: The overall incidence for the prothrombin G20210A gene mutation in the pre-eclamptic group was 3.6% (95% CI 1.2–8.2%) which was not significantly different from the control group 2.5% (95% CI 0.5–7.2%) (p = 0.73, OR 1.44, 95% CI 0.34–6.17). Conclusion: This study provides little evidence of a significant relationship between the prothrombin G20210A gene mutation and pre-eclampsia. Based on our results, we do not recommend testing for the prothrombin G20210A mutation in the routine investigation of women with pre-eclampsia.

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Section: Discussioncontrasting

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Prothrombin G20210A Mutation: Is It Associated with Pre-Eclampsia?

Higgins¹,

Kaiser²,

Moses³

et al. 2000

Gynecol Obstet Invest

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“…Although several studies have demonstrated that serious obstetrical complications, such as thromboembolic disease, pre-eclampsia, abruptio placentae, IUGR or stillbirth, were frequently associated with these mutations [6][7][8][9][10][11][12][13][14][15][16], only one study [17] has investigated exclusively the prevalence of FVL in women with HELLP syndrome. Most recently, Benedetto et al [16] reported a higher FVL prevalence in a subgroup of women with HELLP syndrome compared with pre-eclamptic women ( Table 1).…”

Section: Introductionmentioning

confidence: 99%

Association of maternal and/or fetal factor V Leiden and G20210A prothrombin mutation with HELLP syndrome and intrauterine growth restriction

et al. 2003

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This study was conducted to investigate the association of maternal and/or fetal factor V Leiden (FVL) and G20210A prothrombin mutation with HELLP syndrome. FVL and G20210A prothrombin mutation were determined using PCR. Sixty-three pregnant women, 36 of them diagnosed with HELLP syndrome, were included in the study. Overall, 68 children were born as a result of these pregnancies and blood sampling was possible in 28 out of 39 children from HELLP patients and 25 out of 29 children from the control women. The prevalence of a maternal FVL was elevated 2-fold in HELLP patients compared with the control women [six out of 36 (16.7%) compared with two out of 27 (7.4%); P =0.282]. None of the HELLP patients and only one woman in the control group was found to be positive for the G20210A prothrombin mutation (P =0.251). The fetal carrier frequency was four out of 28 compared with three out of 25 for FVL (P =0.811), and two out of 28 compared with one out of 25 for G20210A prothrombin mutation (P =0.629). Intrauterine growth restriction (IUGR) was significantly higher in fetuses found to be positive for a thrombophilic mutation (P =0.022). IUGR occurred in seven out of ten fetuses with a thrombophilic mutation compared with 11 out of 43 in fetuses without a mutation. The prevalence of FVL, but not of the G20210A prothrombin mutation, seems to be elevated in women with HELLP syndrome. A fetal thrombophilic mutation does not contribute significantly to the clinical features of the HELLP syndrome. Our results demonstrate a fetal contribution to IUGR. Fetal thrombophilic mutations may lead to placental microthrombosis, which consecutively could lead to a disturbed fetoplacental blood flow and thus cause growth restriction.

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“…FV is activated by selective proteolytic cleavage that removes the large B domain, and FVa is inactivated by activated protein C (APC) (Rosing and Tans 1997). Association between preeclampsia and the Leiden mutation in F5 has been reported several times (Dizon-Townson et al 1996;Grandone et al 1997;Mimuro et al 1998;Nagy et al 1998b;Rigo et al 2000). The Leiden mutation is a single base mutation in the F5 gene that results in an amino acid substitution (R506Q) at a predominant APC-cleavage site and is a risk factor for familial venous thrombosis (Rosing and Tans 1997).…”

Section: Introductionmentioning

confidence: 99%

Association analysis of nine missense polymorphisms in the coagulation factor V gene with severe preeclampsia in pregnant Japanese women

et al. 2002

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The Leiden mutation in the coagulation factor V (F5) gene associated with preeclampsia in Caucasians has not been found in Japanese populations. We examined the association of 20 missense polymorphisms in the F5 gene in 133 pregnant Japanese women with preeclampsia and in 224 unrelated, healthy, pregnant Japanese women. Among nine polymorphisms identified in the subjects, the M385T and R485K polymorphisms were associated with preeclampsia (P ϭ 0.05 and P ϭ 0.02, respectively). Haplotype analysis indicated that the R485K polymorphism is truly associated with preeclampsia, whereas the association of the M385T polymorphism is due to linkage disequilibrium. Taken together with reports that the R485 allele yields poor factor V function in comparison with that of the K485 allele and that the F5 Leiden mutation is associated with preeclampsia in Caucasian populations, the findings of the present study suggest that the F5 gene is associated with preeclampsia in pregnant Japanese women.

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Changes of Resistance to Activated Protein C in the Course of Pregnancy and Prevalence of Factor V Mutation

Cited by 12 publications

References 0 publications

Prothrombin G20210A Mutation: Is It Associated with Pre-Eclampsia?

Prothrombin G20210A Mutation: Is It Associated with Pre-Eclampsia?

Association of maternal and/or fetal factor V Leiden and G20210A prothrombin mutation with HELLP syndrome and intrauterine growth restriction

Association analysis of nine missense polymorphisms in the coagulation factor V gene with severe preeclampsia in pregnant Japanese women

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