Association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriage
Abstract Background Inherited thrombophilia (IT) has a complex pathophysiology and is associated with recurrent miscarriage (RM) by causing placental insufficiency and inhibiting fetal development. However, thrombophilia screening in unexplained RM cases is still questionable. This study aimed to in...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | Thrombosis Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12959-024-00587-7 |
| _version_ | 1797273562733608960 |
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| author | Ayman A. Najjar Imam Hassouna Mahmoud A. Srour Hany M. Ibrahim Randa Y. Assi Heba M. Abd El Latif |
| author_facet | Ayman A. Najjar Imam Hassouna Mahmoud A. Srour Hany M. Ibrahim Randa Y. Assi Heba M. Abd El Latif |
| author_sort | Ayman A. Najjar |
| collection | DOAJ |
| description | Abstract Background Inherited thrombophilia (IT) has a complex pathophysiology and is associated with recurrent miscarriage (RM) by causing placental insufficiency and inhibiting fetal development. However, thrombophilia screening in unexplained RM cases is still questionable. This study aimed to investigate the association between the common eight IT mutations and their combinations among Palestinian women with unexplained RM. Methods This is an unmatched case-control study with 200 women (100 unexplained RM cases, 100 controls). Eight common IT mutations namely Factor V Leiden (FVL), prothrombin gene (FII) G202120A, Methylenetetrahydrofolate Reductase (MTHFR) gene (C677T and A1298C), B-fibrinogen gene − 455G > A, FV HR2 A4070G, Plasminogen activator inhibitor 1 (PAI1) 5G/4G and Factor XIIIA (FXIIIA) V34L; were analyzed. The first five mutations were analyzed by Restriction Fragment Length Polymorphism PCR and the other three mutations were analyzed using Amplification Refractory Mutation System PCR. Results The prevalence of the eight IT mutations among the control group was in the order PAI1 5G/4G (69%), MTHFR C677T (53%) and A1298C (47%), BFG − 455G > A (35%), FVL and FV HR2 (each 18%), FXIIIA V34L (16%) and FII G20210A (3%). Patients had a higher percentage of MTHFR A1298C (heterozygotes and mutant homozygote) compared to controls (p = 0.016). Frequencies of mutant alleles MTHFR A1298C (p < 0.001) and FXIIIA V34L (p = 0.009) were higher among patients compared to controls. No significant differences were observed for all other mutations or mutant alleles. Most patients (75%) and controls (75%) have 2–4 mutant alleles out of 8 mutant alleles studied, while 1% of patients and 2% of controls have zero mutant alleles. None of the combinations of the most often studied mutations (FVL, FII G20210A, MTHFR C1677T, and MTHFR A1298C) showed a significant difference between patients and controls. Conclusions There was a significant association between unexplained RM and the mutant alleles of MTHFR A1298C and FXIIIA V34L. No significant association was observed between unexplained RM and the combination of both mutant alleles for the mutations studied. This study is the first Palestinian report that evaluates eight inherited thrombophilia mutations and their alleles’ combinations in unexplained RM cases. |
| first_indexed | 2024-03-07T14:46:10Z |
| format | Article |
| id | doaj.art-e3919e7756ed4722b8aeb84435ca6af9 |
| institution | Directory Open Access Journal |
| issn | 1477-9560 |
| language | English |
| last_indexed | 2024-03-07T14:46:10Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Thrombosis Journal |
| spelling | doaj.art-e3919e7756ed4722b8aeb84435ca6af92024-03-05T20:00:13ZengBMCThrombosis Journal1477-95602024-02-0122111110.1186/s12959-024-00587-7Association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriageAyman A. Najjar0Imam Hassouna1Mahmoud A. Srour2Hany M. Ibrahim3Randa Y. Assi4Heba M. Abd El Latif5Physiology Unit, Zoology Department, Faculty of Science, Menoufia UniversityPhysiology Unit, Zoology Department, Faculty of Science, Menoufia UniversityDepartment of Biology and Biochemistry, Faculty of Science, Birzeit UniversityPhysiology Unit, Zoology Department, Faculty of Science, Menoufia UniversityDepartment of Obstetrics & Gynecology, Faculty of Medicine, Al-Quds UniversityPhysiology Unit, Zoology Department, Faculty of Science, Menoufia UniversityAbstract Background Inherited thrombophilia (IT) has a complex pathophysiology and is associated with recurrent miscarriage (RM) by causing placental insufficiency and inhibiting fetal development. However, thrombophilia screening in unexplained RM cases is still questionable. This study aimed to investigate the association between the common eight IT mutations and their combinations among Palestinian women with unexplained RM. Methods This is an unmatched case-control study with 200 women (100 unexplained RM cases, 100 controls). Eight common IT mutations namely Factor V Leiden (FVL), prothrombin gene (FII) G202120A, Methylenetetrahydrofolate Reductase (MTHFR) gene (C677T and A1298C), B-fibrinogen gene − 455G > A, FV HR2 A4070G, Plasminogen activator inhibitor 1 (PAI1) 5G/4G and Factor XIIIA (FXIIIA) V34L; were analyzed. The first five mutations were analyzed by Restriction Fragment Length Polymorphism PCR and the other three mutations were analyzed using Amplification Refractory Mutation System PCR. Results The prevalence of the eight IT mutations among the control group was in the order PAI1 5G/4G (69%), MTHFR C677T (53%) and A1298C (47%), BFG − 455G > A (35%), FVL and FV HR2 (each 18%), FXIIIA V34L (16%) and FII G20210A (3%). Patients had a higher percentage of MTHFR A1298C (heterozygotes and mutant homozygote) compared to controls (p = 0.016). Frequencies of mutant alleles MTHFR A1298C (p < 0.001) and FXIIIA V34L (p = 0.009) were higher among patients compared to controls. No significant differences were observed for all other mutations or mutant alleles. Most patients (75%) and controls (75%) have 2–4 mutant alleles out of 8 mutant alleles studied, while 1% of patients and 2% of controls have zero mutant alleles. None of the combinations of the most often studied mutations (FVL, FII G20210A, MTHFR C1677T, and MTHFR A1298C) showed a significant difference between patients and controls. Conclusions There was a significant association between unexplained RM and the mutant alleles of MTHFR A1298C and FXIIIA V34L. No significant association was observed between unexplained RM and the combination of both mutant alleles for the mutations studied. This study is the first Palestinian report that evaluates eight inherited thrombophilia mutations and their alleles’ combinations in unexplained RM cases.https://doi.org/10.1186/s12959-024-00587-7Inherited thrombophilia mutationsRecurrent miscarriagePrevalenceWomenPalestine |
| spellingShingle | Ayman A. Najjar Imam Hassouna Mahmoud A. Srour Hany M. Ibrahim Randa Y. Assi Heba M. Abd El Latif Association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriage Thrombosis Journal Inherited thrombophilia mutations Recurrent miscarriage Prevalence Women Palestine |
| title | Association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriage |
| title_full | Association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriage |
| title_fullStr | Association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriage |
| title_full_unstemmed | Association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriage |
| title_short | Association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriage |
| title_sort | association of inherited thrombophilia mutations and their combinations among palestinian women with unexplained recurrent miscarriage |
| topic | Inherited thrombophilia mutations Recurrent miscarriage Prevalence Women Palestine |
| url | https://doi.org/10.1186/s12959-024-00587-7 |
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