Association of inherited thrombophilia gene polymorphism with sporadic and recurrent miscarriages

Aim. Despite numerous scientific studies of possible causes of miscarriage, their etiology remains unclear in approximately 50% of cases. Investigate the prevalence of thrombophilia associated gene polymorphism FGB 455G/A, FII 20210 G/A, FV 1691G/A, ITGA2 807C/T, PAI-1 5G/4G and MTHFR 677C/T in women with sporadic and recurrent miscarriages. Methods. Group I included 35 women with sporadic miscarriage (SM), group II consisted of 57 women with recurrent miscarriage (RM) and 55 women of control group. Genetic testing was performed by PCR-RFLP. Results. In group I of women with SM the 455GA genotype of the FGB gene was more common and its presence in the genotype increases the risk of SM by 4 times and the presence of the 455A allele by 2 times. The Leiden mutation increases the risk of SM by 5 times. In II group of women with RM, the frequency of the 455 AA genotype of the FGB gene was more prevalent and the risk of RM was increased 2.5 times. It is shown that the risk of RM increases 4 times in the presence of the Leiden mutation. The 4G allele of the PAI-1 5G/4G polymorphism leads to a 2-fold increase in the risk of RM, and the presence of the 677TT genotype of the MTHFR gene increases the risk of RM by 3 times. Conclusions. Genetic factors of inherited thrombophilia alleles 455A of the FGB gene, 1691A of the FV gene, 4G of the PAI-1 gene and 677T of the MTHFR gene are alleles of significant risk of reproductive losses both sporadic and, to a greater extent, recurrent. Keywords: sporadic miscarriage, recurrent.miscarriage, inherited thrombophilia, genetic polymorphism.

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Recurrent Miscarriage and Consanguinity among Omani Women– A Cross Sectional Study

Gynecology & Reproductive Health ◽

10.33425/2639-9342.1141 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Fatma Al Hoqani ◽

Wadha Al Ghafri ◽

Saneya El tayeb ◽

Yahya Al Farsi ◽

Vaidyanathan Gowri

Keyword(s):

Recurrent Miscarriage ◽

Cross Sectional Study ◽

University Hospital ◽

Control Group ◽

P Value ◽

Cross Sectional ◽

Recurrent Miscarriages ◽

Sultan Qaboos University ◽

Chi Squared ◽

History Of

Objective: to determine the prevalence of explained and unexplained recurrent miscarriages (RM) and to find out if there is a significant relationship between recurrent miscarriages and consanguinity. Methods: A cross sectional in which the cases group included all women with RM attending the outpatient clinic at Sultan Qaboos University Hospital from July 2006 to April 2012 and the controls group included women with no history of RM after matching them with cases for age (case to control ratio was 1:1). The main outcome measures were the prevalence of consanguinity in women with or without recurrent miscarriages. Results: During study period a total of 290 women with RM were seen. Of which, 150 (51.7%) women had unexplained RM. Control group with no history of RM were 300 women. Consanguinity rate among cases (49.5%) %) was less than the controls (52.7 %%). Both first cousin and second cousin marriages were more common in the controls than the cases and it was not statistically significant (p value 0.476, chi squared test). Conclusion: In this study we found that more than half of RM cases were unexplained and there was no significant association between RM and consanguinity.

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The Genetic Variants of IKZF1 Gene Linked with the Growing Risk of Childhood Acute Lymphoblastic Leukaemia

Current Molecular Medicine ◽

10.2174/1566524019666190219123900 ◽

2019 ◽

Vol 19 (1) ◽

pp. 32-39

Author(s):

Safaa I. Tayel ◽

Sally M. El-Hefnway ◽

Wafaa Moustafa M. Abo El-fotoh ◽

Rania S. El-Zayat

Keyword(s):

Acute Lymphoblastic Leukaemia ◽

Lymphoblastic Leukaemia ◽

Genetic Variants ◽

Transferrin Saturation ◽

Significant Risk ◽

Control Group ◽

Childhood Acute Lymphoblastic Leukaemia ◽

Group I ◽

Egyptian Children ◽

Significant Difference

Background: The zinc finger protein IKAROS (IKZF1) is an essential transcription factor in haematopoiesis that is involved primarily in lymphoid tissue differentiation. Many studies have indicated that IKZF1 alterations may be associated with acute lymphoblastic leukaemia, but the results remain controversial. Objective: We aimed to investigate the association of the rs4132601 T/G and rs10272724 T/C IKZF1 gene polymorphisms with the risk of childhood acute lymphoblastic leukaemia and to determine whether these genetic variants affect the clinical parameters and the iron profiles of these children cohort. Methods: This case control study was conducted on 170 Egyptian children comprising of two groups: group (I) included 90 children diagnosed with acute lymphoblastic leukaemia and group (II) comprised of 80 ages and sex-matched healthy control children. The studied polymorphisms were genotyped using PCR restriction fragment length polymorphism (PCR-RFLP). Results: A higher frequency of the mutant GG genotype and G allele of rs4132601 was found in the patient group than in the control group. The results also showed a significant difference among the rs10272724 genotypes, with a higher frequency of the mutant CC genotype and C allele in the patients than in controls. The mutant GG genotype of rs4132601 and the mutant CC genotype of rs10272724 were associated with a higher serum ferritin level and transferrin saturation and an older age at diagnosis of acute lymphoblastic leukaemia than the other genotypes. Conclusion: IKZF1 rs4132601 and rs10272724 could be considered significant risk contributors to childhood acute lymphoblastic leukaemia and may impact the iron profiles in these children.

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Inherited Thrombophilia and Pregnancy Complications: Should We Test?

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0038-1657782 ◽

2018 ◽

Vol 45 (01) ◽

pp. 050-060 ◽

Cited By ~ 5

Author(s):

Mike Makris ◽

Deepa Arachchillage

Keyword(s):

Pregnancy Outcome ◽

Health Care Professionals ◽

Pregnancy Complications ◽

Recurrent Miscarriage ◽

Late Pregnancy ◽

Inherited Thrombophilia ◽

Recurrent Miscarriages ◽

Conflicting Evidence ◽

Recurrent Pregnancy Losses ◽

Additional Therapy

AbstractRecurrent miscarriages and pregnancy-related complications cause significant stress to couples looking for successful pregnancy outcome as well as to health care professionals. There is conflicting evidence with respect to the presence and the strength of associations between inherited thrombophilia and these complications. A complete thrombophilia screen is expensive, and no proven effective treatment for women with recurrent miscarriage and inherited thrombophilia is currently available. Based on the concept of microvascular thrombosis of the placenta, women with recurrent miscarriage and placenta-related complications frequently get treated with antithrombotic therapy. In this narrative review, the authors explore the evolving understanding and evidence of inherited thrombophilia in recurrent miscarriages and other pregnancy complications, and whether antithrombotic treatment would modify pregnancy outcome in women with inherited thrombophilia. Finally, they provide some personal recommendations based on available evidence for clinical practice. In summary, inherited thrombophilia testing is not required outside a clinical trial for women with recurrent pregnancy losses or late pregnancy complications. The presence of thrombophilia markers does not generally indicate additional therapy during pregnancy, even if a heritable thrombophilic defect is found in women with recurrent miscarriages or late pregnancy complications.

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The contribution of Hind III C>G PAI-1 gene polymorphism in etiology of recurrent miscarriages

Ginekologia Polska ◽

10.17772/gp/2073 ◽

2015 ◽

Vol 86 (4) ◽

pp. 274-279 ◽

Cited By ~ 1

Author(s):

Magdalena Barlik ◽

Hubert Wolski ◽

Krzysztof Drews ◽

Wojciech Pieńkowski ◽

Andrzej Klejewski ◽

...

Keyword(s):

Gene Polymorphism ◽

Recurrent Miscarriages ◽

Pai 1

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Detection of Methylene Tetrahydrofolate Reductase Gene Polymorphism (C677T) In Sudanese Patients with Chronic Myeloid Leukemia

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v9i6.3693 ◽

2019 ◽

Vol 9 (6) ◽

pp. 162-168

Author(s):

Negood Abdelhameed Osman ◽

Alsadig Gassoum ◽

Sanabel Alhussien Ahmed ◽

Nihad Elsadig Babiker

Keyword(s):

Chronic Myeloid Leukemia ◽

Gene Polymorphism ◽

Chronic Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Myeloid Leukemia ◽

White Blood Cells ◽

Mthfr Gene ◽

Control Group ◽

Rt Pcr ◽

Mthfr Gene Polymorphism

Chronic myeloid leukaemia (CML) is a kind of cancer that affects the white blood cells and resort to progress slowly through many years. It’s occur at any age, but is most common in older (60-65 years) of age. This is a cross sectional study aimed to detect MTHFR gene polymorphism (C677T) among Sudanese patients diagnosed with Chronic Myeloid Leukaemia and conducted at the research laboratory of the national center of neurological sciences (NCNS), Khartoum, Sudan.50 patients with Chronic Myeloid Leukemia (CML) diagnosed as BCR-ABL positive by RT-PCR used as a cases and 50 apparently healthy individuals as a control. A 5 ml of blood samples were collected in EDTA anticoagulant container for DNA Extraction and white blood cells count, hemoglobin level and platelets count. Genotyping of the MTHFR was carried out using PCR technique and the SNP (C677T) confirmed by sequencing a subset of samples. The results were analyzed using bioinformatics tools. The results showed; the most affected age group in the patients was 51-60 years followed by 41-50 years which constituted 32% and 30%, respectively. The hematological findings revealed that, the mean of TWBCs was 47.4, HB was 11.9 for patients, 7.2 and 14.1 respectively for control group (P = 0.000). PLT was 313.5 for patients and 287.5 for control group (P = 0.187). MTHFR gene was detected in the all patients (198pb) by the PCR, Sequence results were aligned with the reference sequence of MTHFR gene, the polymorphic C >T was found to be matched with the registered mutation in NCBI data base. This study provides the first evidence for associations of MTHFR gene polymorphism with the risk of chronic myeloid leukemia in Sudanese patients. The C >T genotype of the rs 677 polymorphism in MTHFR gene may have a promoting effect on chronic myeloid leukemia. Keywords: Chronic myeloid leukaemia (CML), DNA, PCR, RT-PCR, MTHFR

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Evaluation of Vitamin D-Binding Protein Gene Polymorphism and its Plasma Concentration in Kurdish Patients With Breast Cancer in Sanandaj, Iran

Avicenna Journal of Medical Biochemistry ◽

10.34172/ajmb.2020.13 ◽

2020 ◽

Vol 8 (2) ◽

pp. 89-93

Author(s):

Roya Moloudinia ◽

Gelavij Mahmoodi ◽

Mohammad Abdi ◽

Sabrieh Amini ◽

Shirin Ferdowsi

Keyword(s):

Breast Cancer ◽

Vitamin D ◽

Gene Polymorphism ◽

Binding Protein ◽

Plasma Concentrations ◽

Significant Risk ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Case Group ◽

Vitamin D Binding Protein

Background: Several studies have indicated that polymorphism in vitamin D pathway genes is associated with breast cancer (BC) risk. Vitamin D-binding protein (VDBP) is a vital element in the metabolism of the vitamin D. VDBP carries the serum 25(OH) D3 to cells to promote vitamin D biological functions, such as cell proliferation and apoptosis. Missense SNP (rs.7041) is a common polymorphism in VDBP gene, which shows ethnic-specific allele frequencies. Objectives: This study presents the correlation of the rs7041 (Asp432Glu) gene polymorphism and plasma concentrations of VDBP in Kurdish patients with BC in Sanandaj, Iran. Methods: This cross-sectional study included 44 premenopausal BC patients and 44 healthy subjects. Plasma VDBP concentration was measured by enzyme-linked immunosorbent assay (ELISA). The VDBP (rs7041) was genotyped by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Results: VDBP level was associated with a non-significant risk of BC (P=0.397). Frequencies of individuals with VDBP (rs7041) TT, TG, and GG genotypes were 13.6%, 52.2%, and 34.09% in case group and 11.3%, 79.5%, and 9.9% in control group, respectively. Genotype GG associated with increased susceptibility to developing BC (odds ratio [OR]=5.172, CI: 1.555-17.2, P=0.007). There was a significant reverse correlation between GT genotype and BC (OR=0.282, 95% CI: 0.110-0.722, P=0.008) Conclusion: The changes in the vitamin D pathway may increase susceptibility to develop BC in the Iranian Kurdish population.

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Gene-gene interactions and prevalence of gene polymorphism associated with disorders of hemostasis and folate metabolism in patients with recurrent miscarriage

GYNECOLOGY ◽

10.26442/20795696.2019.2.190345 ◽

2019 ◽

Vol 21 (2) ◽

pp. 18-22

Author(s):

Nataly I Frolova ◽

Tatiana E Belokrinitskaya ◽

Nataliya N Strambovskaya ◽

Evgeniya P Belozertseva

Keyword(s):

Pregnant Women ◽

Spontaneous Abortion ◽

Early Pregnancy ◽

Gene Polymorphisms ◽

Recurrent Miscarriage ◽

Gene Interaction ◽

Control Group ◽

Minor Alleles ◽

History Of ◽

Pai 1

Aim. To assess the association between polymorphisms of FVL-1691G>A, FII-20210G>A, MTHFR-677C>T, MTHFR-1298А>C, РАІ-1-6755G>4G and their combinations in patients with recurrent early pregnancy losses (RPL). Materials and methods. This study included two groups of women (age range 20-35 years): 50 currently non-pregnant women with a history of 2-5 unexplained recurrent early spontaneous abortion and unknown causes of miscarriages (RPL group), and 50 currently non-pregnant women with a history of having given birth to at least one live baby and without a history of spontaneous abortion, preterm labor, stillbirth, preeclampsia and other pregnancy complications (control group). Gene polymorphisms were detected by the technique of polymerase chain reaction-real time. We have analyzed the frequencies, Hardy-Weinberg equilibrium, V-Kramer test, χ2 test, odds ratio (OR) and its 95% confidence interval (95% CI). General (χ2 test, df=2) and multiplicative (χ2 test, df=1) models of inheritance have been used to assess the presence of gene polymorphisms. Results. Significant association between heterozygotes genotype PAI-1-5G4G (72% vs 32%, p=0.000; OR 5.46; 95% CI 2.32-12.87) and RPL was found. Heterozygous genotype FII-20210GA was detected only in RPL group (4% vs 0%). Combinations of genetic polymorphisms of FVL-1691G>A, FII-20210G>A, MTHFR-677C>T, MTHFR-1298А>C, РАІ-1-6755G>4G increase the risk of RPL by 2.4 times (56% vs 20%; χ2=29.20, р=0.000; OR 3.69, 95% CI 1.52-8.97; strong V-Kramer association). The combination of two heterozygotes variants of minor alleles was found to be a risk factor for RPL (34% vs 10%; χ2=8.73, р=0.004; OR 4.64, 95% CI 1.55-3.84). Combined PAI-1-5G4G + FVL-1691GA genotypes was detected only in RPL group of women (2% vs 0%). No significant association between the combination of three heterozygotes variants of minor alleles and RPL. Conclusion. Our data suggest significant gene-gene interaction of the heterozygotes variants of minor alleles of FVL-1691G>A, FII-20210G>A, MTHFR-677C>T, MTHFR-1298А>C, РАІ-1-6755G>4G polymorphisms in patients with recurrent miscarriage. Combined genotypes FVL-1691GA/PAI-1-5G4G can be considered as a genetic molecular predictor of recurrent early pregnancy losses.

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Serum Homocysteine, Vitamin B12, Folic Acid Levels and Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphism in Vitiligo

Disease Markers ◽

10.1155/2012/540597 ◽

2012 ◽

Vol 33 (2) ◽

pp. 85-89 ◽

Cited By ~ 12

Author(s):

Ali Yasar ◽

Kamer Gunduz ◽

Ece Onur ◽

Mehmet Calkan

Keyword(s):

Folic Acid ◽

Gene Polymorphism ◽

Vitamin B12 ◽

Significant Relationship ◽

Gene Polymorphisms ◽

Serum Vitamin ◽

Mthfr Gene ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Mthfr Gene Polymorphism

The aim of this study was to determine serum vitamin B12, folic acid and homocysteine (Hcy) levels as well as MTHFR (C677, A1298C) gene polymorphisms in patients with vitiligo, and to compare the results with healthy controls. Forty patients with vitiligo and 40 age and sex matched healthy subjects were studied. Serum vitamin B12 and folate levels were determined by enzyme-linked immunosorbent assay. Plasma Hcy levels and MTHFR polymorphisms were determined by chemiluminescence and real time PCR methods, respectively. Mean serum vitamin B12 and Hcy levels were not significantly different while folic acid levels were significantly lower in the control group. There was no significant relationship between disease activity and vitamin B12, folic acid and homocystein levels. No significant difference in C677T gene polymorphism was detected. Heterozygote A1298C gene polymorphism in the patient group was statistically higher than the control group. There was no significant relationship between MTHFR gene polymorphisms and vitamin B12, folic acid and homocysteine levels. In conclusion, vitamin B12, folate and Hcy levels are not altered in vitiligo and MTHFR gene mutations (C677T and A1298C) do not seem to create susceptibility for vitiligo.

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Anti-annexin V Antibodies in Women with Recurrent Miscarriage

Clinical Medicine Insights Reproductive Health ◽

10.4137/cmrh.s5835 ◽

2010 ◽

Vol 4 ◽

pp. CMRH.S5835

Author(s):

M.N. EL-Gharib ◽

T.M. Elhawary ◽

S.H. Elshourbagy ◽

M.A. Morad

Keyword(s):

Pregnant Women ◽

Recurrent Miscarriage ◽

Characteristic Curve ◽

Annexin V ◽

Mean Value ◽

Control Group ◽

Etiologic Factor ◽

Group I ◽

History Of ◽

The Mean

Objective To determine the role of anti-annexin V antibodies (a-A5) as an etiologic factor in recurrent pregnancy failure. Study design Prospective observational study. Material and methods The study included ninety first trimester pregnant women who had a history of unexplained recurrent miscarriage (group I) with ninety well-matched pregnant women with a history of normal reproductive outcome allocated as control group (GII) and another ninety nonpregnant women (GIII). Sera from all women controls were analyzed for anti-annexin antibody measured by Elisa. Results The mean value of a-A5 was 11.37 ± 6.78, 7.7 ± 1.40 and 6.20 ± 0.95 ng/ml in groups I, II and III respectively. There was a significant increase in the mean value a-A5 among women with a history of recurrent miscarriage, compared with controls. The mean value was 13.92 ± 2.42 ng/ml among patients with unfavourable outcome, compared with a corresponding value of 6.95 V 0.58 ng/ml among women with favourable outcome. The receiver operator characteristic curve revealed that the cutoff value of a-A5 was 8.61 ng/ml. Conclusion This study emphasizes the relationship between anti-annexin V antibodies and recurrent miscarriage.

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Prevalence of the polymorphism MTHFR A1298C and not MTHFR C677T is related to chromosomal aneuploidy in Brazilian Turner Syndrome patients

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302008000800028 ◽

2008 ◽

Vol 52 (8) ◽

pp. 1374-1381 ◽

Cited By ~ 15

Author(s):

Kelly Cristina de Oliveira ◽

Bianca Bianco ◽

Ieda T. N. Verreschi ◽

Alexis Dourado Guedes ◽

Bianca Borsato Galera ◽

...

Keyword(s):

Gene Polymorphism ◽

Turner Syndrome ◽

Mthfr C677t ◽

Mthfr Gene ◽

Control Group ◽

Dna Hypomethylation ◽

Chromosome Mosaicism ◽

Chromosomal Aneuploidy ◽

Mthfr Gene Polymorphism ◽

History Of

BACKGROUND: Dysfunctions in the folate metabolism can result in DNA hypomethylation and abnormal chromosome segregation. Two common polymorphisms of this enzyme (C677T and A1298C) reduce its activity, but when associated with aneuploidy studies the results are conflicting. The objective of the present study is to analyze the MTHFR gene polymorphisms in women with Turner Syndrome and in a control group, correlating the findings to the chromosomal aneuploidy. METHODS: The study comprised 140 patients with Turner Syndrome, of which 36 with chromosome mosaicism and 104 non-mosaics, and a control group of 209 fertile and healthy women without a history of any offspring with aneuploidy. Polymorphisms C677T and A1298C were studied by RFLP-PCR and the results were statistically analyzed. RESULTS: The frequency of genotypes MTHFR 677CC, 677CT and 677TT in the patients with Turner Syndrome and chromosome mosaicism was, respectively, 58.3%, 38.9% and 2.8%. Among the patients with non-mosaic Turner Syndrome, 47.1% presented genotype 677CC, 45.2% genotype 677CT, and 7.7% genotype 677TT. Among the 209 individuals of the control group, genotypes 677CC, 677CT and 677TT were found at the following frequencies: 48.3%, 42.1% and 9.6%, respectively. As for polymorphism A1298C, the patients with Turner Syndrome and chromosome mosaicism presented genotypes 1298AA, 1298AC and 1298CC at the following frequencies: 58.3%, 27.8% and 13.9%, respectively. Among the non-mosaic Turner Syndrome patients, genotype 1298AA was found in 36.5%, genotype 1298AC in 39.4%, and genotype 1298CC in 22.1%. In the control group, genotypes 1298AA, 1298AC and 1298CC were present at the following frequencies: 52.6%, 40.7% and 6.7%, respectively. CONCLUSION: No correlation was observed between the MTHFR gene polymorphism 677 and chromosomal aneuploidy in the Turner Syndrome patients. However, the MTHFR gene polymorphism at position 1298, mainly genotype 1298CC that reduces the enzyme efficiency, was more frequent in the group of Turner Syndrome patients, suggesting its involvement in mechanisms related to chromosomal imbalances.

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