<i>JAK2</i>V617F Mutation in Unexplained Loss of First Pregnancy

Mercier, É.; Lissalde-Lavigne, Géraldine; Gris, Jean‐Christophe

doi:10.1056/nejmc071528

Cited by 38 publications

(30 citation statements)

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“…The presence of high incidence of thromboembolic attacks due to JAK2V617F gene mutation and pregnancy loss in obese women and a possible relationship between these parameters is a matter of concern. In this study women who were positive for JAK2V617F mutation in the case group represented 9.3 % versus the control group who were negative for mutation (p<0.001) Mercier et al, (2007) supported this results that the mutation was present more frequently in patients with past history of pregnancy loss (1.06%) than in control group (0.20%). Also Melillo et al, (2009) stated that fetal loss encountered more in females with the JAK2 V617F mutation (mutated vs. unmutated: 36.0% vs. 8.3%, P< 0.037), and this correlation was further confirmed by multivariate analysis (OR: 6.19; 95% CI: 1.17-32.61, P < 0.038).…”

Section: Discussionsupporting

confidence: 84%

“…(El Hachem et al, 2017) It is recorded that the disorders which promote to venous thrombosis, are all named "thrombophilias," which have a role in the pathogenesis or the process of fetal loss. The great differences between theories as well as keeping in mind the correlation between such disorders and unexplained pregnancy loss suggests the presence of underlying risk modifiers (Mercier et al ., 2007). The included women in the present study had at least one history of live birth, to rule out any anatomical factor that might be a cause for the repeated losses.…”

Section: Discussionmentioning

confidence: 99%

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2018

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Maternal obesity is one of the factors that have a role in recurrent pregnancy loss (RPL). This research deals with fetal loss in obese pregnant women that might be due the mutation in Janus kinase2 gene (V617F). The main purpose of this article is to explore the association of obesity with JAK2 V617F mutation in recurrent pregnancy loss. This study is carried out on 250 women, the case group with a history of recurrent pregnancy loss and a body mass index (BMI) >24.9kg/m 2 . Control group consists of women with normal body mass index and have at least one live child and with no history of pregnancy loss. All subjects were investigated for the mutations by using the allele-specific multiplex PCR. Women in the study who were obese and tested positive for JAK2 V617F were 14 %. 9.3% of patients in the case had a BMI with mean of 30.9 ±4.3. In conclusion the study suggests a correlation between the increased risk for the occurrence of RPL in obese women and the investigated V617F mutation in the Jak2 gene exon 12, this research demonstrates the feasibility that obesity could be a modifiable risk factor for that somatic mutation.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

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2018

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“…Unfortunately, in that study no exhaustive list of risk factors for pregnancy loss was provided in 159 (41%) of the included women. In contrast to our observation, a large previous study found a prevalence of 1% in women with a single unexplained pregnancy loss [5]. However, the positive test results in that study were not confirmed by repeated analyses.…”

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confidence: 99%

“…In vitro gene promoter studies identified functional HNF4a binding sites near the genes encoding human procoagulant factors (F) II (F2), VII (F7), VIII (F8), IX (F9), X (F10), XI (F11), XII (F12) [1][2][3][4][5][6][7], and anticoagulant factors protein S (PROS1), protein Z (PROZ) and antithrombin III (SERPINC1) [8][9][10]. The in vivo importance of HNF4a in regulating hepatic transcription of procoagulant genes was established by examining hepatic mRNA levels from liver-specific HNF4a-null mice [11].…”

Section: Disclosure Of Conflict Of Interestsmentioning

confidence: 99%

Prevalence of JAK2V617F mutation in women with unexplained recurrent miscarriage

Kaandorp

Lauw

Schoot

et al. 2010

Journal of Thrombosis and Haemostasis

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To cite this article: Kaandorp SP, Lauw MN, van der Schoot CE, Goddijn M, van der Veen F, Koene HR, Biemond BJ, Middeldorp S. Prevalence of JAK2V617F mutation in women with unexplained recurrent miscarriage. J Thromb Haemost 2010; 8: 2837-9.The incidence of recurrent miscarriage (RM) amongst couples trying to conceive varies between 1% and 5% [1]. In 50-60% of couples the RM remains unexplained, even after thorough diagnostic evaluation. Therefore, the search for etiologic factors is very important for the couples and clinician alike.Polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF) belong to the group of Philadelphia-chromosome negative myeloproliferative disorders (MPD). Pregnant women with MPD have an increased risk of pregnancy complications. Women with ET have a 3.4-fold (OR, 3.4; 95% CI, 3.0-3.9) increased risk of experiencing pregnancy loss (first trimester miscarriage, second trimester miscarriage and stillbirth) as compared with the general population [2]. Although the pathogenesis of the increased pregnancy loss is unclear, thrombotic complications, frequently observed in patients with PV and ET, are likely to play a role [3].Recently, a somatic gain-of-function mutation associated with the group of MPD was found in exon 14 of the JAK2 gene [4]. The JAK2V617F mutation is found in virtually all patients with PV and in half of patients with ET and IMF.In a large case-control study of 3496 women with pregnancy loss in the first pregnancy (first trimester miscarriage, second trimester miscarriage and stillbirth) the prevalence of the JAK2V617F mutation was significantly higher in cases than in controls with a single uncomplicated pregnancy (1.1% vs. 0.2%; OR, 5.3; 95% CI, 2.4-11.9) [5]. In contrast to these findings, in a cohort of 389 women with RM, no JAK2V617F mutations were observed (0.0%; 95% CI, 0-0.009%) [6]. In view of these discordant data, we aimed to assess prevalence of the JAK2V617F mutation in a well-defined group of women with unexplained RM.We included consecutive women who consulted our recurrent miscarriage clinic between October 2005 and November 2007 at the Academic Medical Center, Amsterdam. Women were eligible if aged between 18 and 42 years and diagnosed with unexplained RM. RM was defined as two or more miscarriages with an upper gestational age of 20 weeks. All women were investigated according to a standardized local protocol (derived from the Dutch guidelines on RM) [7]. Unexplained RM was diagnosed in the case of normal parental karyotypes of both partners, the absence of uterine pathology on pelvic ultrasound, absence of antiphospholipid syndrome (lupus anticoagulant and anticardiolipin IgG and IgM), and a normal fasting level of homocysteine (lower than 16 lmol L )1). Participating women were tested for inherited thrombophilia, but the presence of factor V Leiden, the prothrombin 20210A mutation, or deficiencies of antithrombin, protein C or S, were not considered an explanation for RM.DNA was isolated from peripheral blood using standar...

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“…The presence of polymorphism V617F G4T in Janus kinase 2 gene JAK2 among the studied SNP is due to the data on a higher frequency pregnancy interruptions caused by thrombosis in women with this mutation [88,89]. However, somatic type of mutation, a clear correlation with age and the low enough prevalence [90] is hardly allow us to speak about the effectiveness of this SNP testing in preparation for IVF.…”

Section: Snps In the Renin-angiotensin Systemmentioning

confidence: 94%

Toward optimal set of single nucleotide polymorphism investigation before IVF

Ivanov

Dedul

Fedotov

et al. 2016

Gynecological Endocrinology

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Background: At present, the patient preparation for IVF needs to undergo a series of planned tests, including the genotyping of single nucleotide polymorphism (SNP) alleles of some genes. In former USSR countries, such investigation was not included in overwhelming majority of health insurance programs and paid by patient. In common, there are prerequisites to the study of more than 50 polymorphisms. An important faced task is to determine the optimal panel for SNP genotyping in terms of price/number of SNP. Materials and methods: During 2009-2015 in the University Hospital of St. Petersburg State University, blood samples were analyzed from 550 women with different reproductive system disorders preparing for IVF and 46 healthy women in control group. In total, 28 SNP were analyzed in the genes of thrombophilia factors, folic acid cycle, detoxification system, and the renin-angiotensin system. The method used was real-time PCR. Results: A significant increase in the frequency of pathological alleles of some polymorphisms in patients with habitual failure of IVF was shown, compared with the control group. As a result, two options defined panels for optimal typing SNP before IVF were composed. Standard panel includes 8 SNP, 5 in thromborhilic factors, and 3 in folic acid cycle genes. They are 20210 G4A of FII gene, R506Q G4A of FV gene (mutation Leiden), -675 5G44G of PAI-I gene, L33P T4C of ITGB3 gene, -455 G4A of FGB gene, 667 C4T of MTHFR gene, 2756 A4G of MTR gene, and 66 A4G of MTRR gene. Extended panel of 15 SNP also includes 807 C4T of ITGA2 gene, T154M C4T of GP1BA gene, second polymorphism 1298 A4C in MTHFR gene, polymorphisms of the renin-angiotensin gene AGT M235T T4C and -1166 A4C of AGTR1 gene, polymorphisms I105V A4G and A114V C4T of detoxification system gene GSTP. Conclusion:The results of SNP genotyping can be adjusted for treatment tactics and IVF, and also medical support getting pregnant. The success rate of IVF is increased as the result, especially in the group with the usual failure of IVF.

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JAK2V617F Mutation in Unexplained Loss of First Pregnancy

Cited by 38 publications

References 5 publications

Untitled

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Prevalence of JAK2V617F mutation in women with unexplained recurrent miscarriage

Toward optimal set of single nucleotide polymorphism investigation before IVF

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