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Background: The main markers for estimation of the tendency for thromboembolic disorders are Factor V Leiden, Prothrombin gene (G20210A), and MTHFR (C677T) polymorphism. Objectives: The aim of the present research is to determine the frequency distribution of genetic mutations of (FV Leiden, Prothrombin II, and MTHFR) genes in patients with early-onset thromboembolic diseases. Materials and Methods: This is a retrospective study done on children and young adults of both sexes aged from 1 to 45 years with thromboembolic disease with no obvious reason who attended patients clinics in Al-Salam Teaching Hospital and were referred from private clinics for a period from June 1, 2019, to August 30, 2020. Detection of gene polymorphism was done in three steps started by isolation of DNA from the blood samples followed by in vitro polymerase chain reaction amplification then hybridization of amplification products at 45°C. Results: A total of 50 cases with thromboembolic diseases were enrolled in this study; 21 (42%) were male and 29 (58%) were female. Patients’ mean age was (26.64 ± 8.68) years. Factor V Leiden mutation was the most frequent mutation (12%) followed by MTHFR (C677T) mutation 6%, and the least frequency was for prothrombin gene mutation G20210A (2%). Conclusion: The prevalence of mutations in gene encoding Factor V Leiden was higher than MTHFR C677T and Prothrombin 20210A polymorphisms in our locality, consequently, assay for mutation of Factor V Leiden must be included in the evaluation of patients with thromboembolic diseases with no obvious cause.

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Recurrent pregnancy loss (RPL) complication is a challenge of reproductive medicine due to its often unknown etiology.A case-control study was carried out between June 2019 and April 2020 to examine the correlation between RPLand inherited thrombophilia (IT), namely mutations in factor V Leiden (FVL G1691A), prothrombin (FII G20210A),and methylenetetrahydrofolate reductase (MTHFR C677T). A total of 120 Lebanese women with RPL was studiedand compared, for the frequency of these mutations, to 100 healthy reproductive Lebanese women. The associationbetween the zygosity status of the three tested mutations, the existence of more than one prothrombotic single nucleotidepolymorphisms (SNPs), and the increased risk of RPL were examined using Chi-square or two-tailed fisher exacttest, and the student t test. The predictive factors of RPL were analyzed using a multiple logistic regression model.P

Abstract Background Breast cancer is considered the leading cause of cancer-related death among Egyptian women (15.41%). One of the common BC risk factors is the genetic factor. One-carbon metabolism is one of the pathways reported to increase BC risk by influencing DNA synthesis and methylation. Methyl tetrahydrofolate reductase (MTHFR), thymidylate synthase (TYMS) and DNA methyltransferase (DNMT) enzymes are key enzymes in one-carbon metabolism directly and through influencing folate metabolism. We aimed to study the association of the gene expression level and polymorphisms of MTHER C677T (rs1801133), TYMS (rs45445694), TYMS 3′UTR 1494del6 and ΔDNMT3B − 149C>T with breast cancer risk in a sample of Egyptian women. Methods This study was conducted on one hundred female breast cancer patients. Genotyping and gene expression of the MTHFR and TYMS (1494del6, rs45445694) and DNMT3B genes were performed. Results There was no significant difference (OR 1.493; 95% CI 0.78–2.84; P = 0.288) in the frequency of the MTHFR (C677T) genotypes between breast cancer patients and control subjects and no significant difference in the frequency of the MTHFR mutant T allele. TYMS tandem repeats showed a significant difference (OR 2.232; CI 1.21–4.12; P = 0.01) in the frequency of the genotype 2R/3R among breast cancer patients and control subjects; however, the frequency of the 2R allele was not significantly different from that of the 3R allele (OR 1.461; 95% CI 0.96–2.21; P = 0.073). TYMS 3′-UTR 1494del6 showed a significant difference in the distribution of (+ 6/ + 6), (+ 6/− 6) and (− 6/− 6) genotypes between the patient and control groups (P ≤ 0.001*), and its corresponding mutant allele showed P value ≤ 0.001, 95% CI = 1.64–3.76 and OR = 2.483. The expression of MTHFR was downregulated by 0.62-fold in all malignant tissues compared to normal adjacent tissues (0.57 ± 0.20, P T) SNP are associated with a high risk of breast cancer and that there is a correlation between the 3′-UTR 1494del6 polymorphism (genotype − 6/− 6) and breast cancer risk. A significant reduction was found in the MTHFR gene expression level in BC compared with control tissues, and the DNMT3B (− 149C>T) SNP did affect the DNMT3B expression level.

Purpose: This study aims to investigate the association between paternal methylenetetrahydrofolate reductase (MTHFR) polymorphisms (C677T) and embryonic development, pregnancy, and neonatal outcomes in intracytoplasmic sperm injection (ICSI) treatment. Methods: A total of 191 infertile men undergoing ICSI treatment at the Reproductive and Genetic Hospital, The First Affiliated Hospital of USTC, were recruited between January 2020 and June 2021. The MTHFR C677T polymorphism genotyping was evaluated in these male patients, and they were stratified into three groups according to genotyping results: Control (CC), heterozygote mutated (CT), and mutated homozygote (TT). In addition, we conducted a comparative analysis of embryonic development, pregnancy, and neonatal outcomes among these three groups. Results: The embryonic development (including normal fertilization rate (80.14% vs. 83.06% vs. 85.10%; p = 0.37), high-quality embryo rate (45.26% vs. 43.69% vs. 46.04%; p = 0.72), blastocyst formation rate (42.47% vs. 43.18% vs. 39.38%; p = 0.62), implantation rate (42.47% vs. 36.25% vs. 41.22%; p = 0.62), and clinical pregnancy rate (64.71% vs. 58.75% vs. 66.67%; p = 0.59) were not comparable among these three groups. Moreover, no significant difference was observed in terms of pregnancy outcomes (including miscarriage rate (24.24% vs. 12.77% vs. 22.5%; p = 0.35) and live birth rate (49.02% vs. 51.25% vs. 51.66%; p = 0.96)). Additionally, no marked difference was observed in terms of neonatal outcome (including, preterm delivery rate (24% vs. 14.63% vs. 9.67%; p = 0.35), birth height (p = 0.75), birth weight (p = 0.35), neonatal sex (p = 0.48), gestational age at delivery (p = 0.24), Apgar score (p = 0.34), and birth defects (0% vs. 2% vs. 9%; p = 0.23) among the study groups. Conclusion: The paternal MTHFR C677T polymorphism is not associated with embryo quality, pregnancy, or neonatal outcomes in ICSI treatment. Therefore, in our population, MTHFR polymorphisms do not provide helpful information in explaining ICSI failure. [ABSTRACT FROM AUTHOR]

Recurrent pregnancy loss (RPL) complication is a challenge of reproductive medicine due to its often unknown etiology. A case-control study was carried out between June 2019 and April 2020 to examine the correlation between RPL and inherited thrombophilia (IT), namely mutations in factor V Leiden (FVL G1691A), prothrombin (FII G20210A), and methylenetetrahydrofolate reductase (MTHFR C677T). A total of 120 Lebanese women with RPL was studied and compared, for the frequency of these mutations, to 100 healthy reproductive Lebanese women. The association between the zygosity status of the three tested mutations, the existence of more than one prothrombotic single nucleotide polymorphisms (SNPs), and the increased risk of RPL were examined using Chi-square or two-tailed fisher exact test, and the student t test. The predictive factors of RPL were analyzed using a multiple logistic regression model. P<0.05 was considered to be statistically significant. Our results showed statistically significant higher frequencies of FVL G1691A and FII G20210A mutations among the cases with RPL compared to the control group. Thus, RPL is associated with FVL G1691A and FII G20210A mutations. These mutations seem to increase the risk of RPL in the Lebanese women. Therefore, we suggest thrombophilia screening and adequate genetic counseling for women with RPL and at high-risk to plan for primary prevention, avoiding thromboembolic or obstetric accidents, and reducing the associated morbidity and mortality among Lebanese women. [ABSTRACT FROM AUTHOR]

Sara Khalife, Nisrine Bissar-Tadmouri Department of Medical Laboratory Technology, Faculty of Health Sciences, Beirut Arab University, Tripoli, LebanonCorrespondence: Sara KhalifeDepartment of Medical Laboratory Technology, Faculty of Health Sciences, Beirut Arab University, Tripoli, LebanonTel +961 70 557389Email sara.khalifeh@bau.edu.lbIntroduction: Factor V Leiden (G1691A), prothrombin (G20210A) and MTHFR (C677T) gene mutations were investigated in many studies for their association with Deep Venous Thrombosis.Case Presentation: A North Lebanese family has been examined, from an index case, a 40-year-old woman, who had a history of venous thrombosis with unexplained recurrent miscarriage. The index case was found to be heterozygous for factor V Leiden G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T gene variants. Her family members were heterozygous for at least two of the three-point mutations, and multiple risk factors associated with thrombophilia were identified.Conclusion: Our findings emphasize the need for clarifying the utility and futility of thrombophilia testing in the era of molecular diagnostics.Keywords: factor V Leiden G1691A, MTHFR C677T, prothrombin G20210A, deep venous thrombosis, recurrent pregnancy loss, Lebanese family

INTRODUCTION[|]Central retinal vein occlusion (CRVO) is a severe eye disease that impairs vision. Although numerous systemic conditions have been reported to be a contributor, its exact pathophysiology has not yet been resolved. The purpose of this study was to study the role of some common thrombophilic polymorphisms in CRVO patients.[¤]METHODS[|]A total of 33 CRVO patients (25 non-ischemic CRVO and 8 ischemic CRVO) and 30 controls were recruited. Factor V Leiden (G1691A), prothrombin (Factor II G20210A), MTHFR (C677T), MTHFR (A1298C), and PAI-1 5G/4G polymorphisms in venous blood DNA samples were examined, as well as the presence of hypertension, diabetes mellitus, glaucoma, smoking, and history of thrombosis.[¤]RESULTS[|]It was determined that MTHFR C677T polymorphisms, either in heterozygous or homozygous form, might be a risk factor for CRVO and systemic thrombosis. No differences were detected between the CRVO and control groups in terms of diabetes mellitus (p=0.058>0.05), hypertension (p=0.3>0.05), smoking (p=0.923>0.05), glaucoma (p=0.06>0.05) or use of anticoagulant drugs (p=0.4>0.05). Analysis of patient history revealed a statistically significant difference regarding a thrombotic event in the medical history of the CRVO group (p=0.001

Background: The MTHFR (methylenetetrahydrofolate reductase) rs1801133 polymorphism leads to higher circulating levels of homocysteine, which is related to several liver diseases. We aimed to evaluate the relationship between MTHFR rs1801133 polymorphism and liver fibrosis progression in HCV-infected patients.Methods: We conducted a preliminary retrospective cohort study in 208 non-cirrhotic HCV-infected patients. These subjects had at least two liver stiffness measurements (LSM), which were assessed using transient elastography, and no patient had cirrhosis at baseline. We analyzed the association between MTHFR rs1801133 and outcome variables using Generalized Linear Models.Results: HCV-infected patients were 47 years old, around 54% were males, a low frequency of high alcohol intake (13.5%) or prior use of intravenous drugs (10.1%). A total of 26 patients developed cirrhosis (LSM1 ≥ 12.5) during a median follow-up of 46.6 months. The presence of the rs1801133 C allele showed an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.90; 95%CI = 0.83–0.98; p = 0.020) and the cirrhosis progression (adjusted OR = 0.43; 95%CI = 0.19–0.95; p = 0.038). Besides, rs1801133 CT/CC genotype had an inverse association with the LSM2/LSM1 ratio (adjusted AMR = 0.80; 95%CI = 0.68–0.95; p = 0.009) and the cirrhosis progression (adjusted OR= 0.21; 95%CI = 0.06–0.74; p = 0.015).Conclusions:MTHFR rs1801133 C allele carriers presented a diminished risk of liver fibrosis progression and development of cirrhosis than rs1801133 T allele carriers. This statement supports the hypothesis that MTHFR rs1801133 polymorphism appears to play a crucial role in chronic hepatitis C immunopathogenesis.

Genetic causes of thrombophilia have been suggested as a possible cause of recurrent pregnancy loss (RPL). Fifty female patients aged between 21- 40 years and experienced at least two times early pregnancy loss were enrolled in the current study. Blood samples were aspirated, infectious (TORCH), hormonal (gonadotrophines, steroids, and thyroid hormones), ultrasonic, and serological (anti-lupus and anti-phospholipid antibodies) evaluations were conducted to exclude any individual candidate who had been suspected to have causes of early pregnancy loss rather than the genetic attribute. DNA from each particular sample was extracted by components of (FVL-PTH and MTHFR)StripAssay®A kit Vienna Lab Diagnostics GmbH, Vienna, Austria).this kit includes three steps: (1) DNA isolation, (2) Multiplex PCR amplification was performed by using biotinylated primers, for detecting different mutations in the three genes of interest (FVL-PTH and MTHFR) (3) Hybridization of amplification products to a test strip containing allele-specific oligonucleotide probes immobilized as an array of parallel lines. The results revealed that 24 samples out of 50 had MTHFR C677T mutations while 2 samples only had FV (G1691A)mutation while prothrombin mutation (G20210A)has not been detected. In conclusion: genetic mutation had significant impact in patients suffered recurrent pregnancy loss.

Thrombophilia may be anticipated by single or combined hereditary defects in encoding genes factor V, Prothrombin, and MTHFR. The aim of this study was to determine the prevalence and associated risks of V Leiden (G1691A), Prothrombin (G20210A), and MTHFR (C677T) mutations in Saudi women with Deep Vein Thrombosis (DVT) and women with recurrent pregnancy loss (RPL). Protein C and protein S activity were measured to determine combined effects, if any. We examined 60 women with a history of DVT and 60 with RPL, extracted DNA from EDTA blood and determined three mutations by using multiplex PCR reactions followed by Strip Assay KIT. Pro C Global assay was used to determine the cutoff value [PCATNR = 0.80]. Protein C/S chromogenic assay was used to estimate protein C and S percentages. Frequency of Factor V Leiden G/A genotype in patients with DVT 7 (11.6%) had a significant association for DVT χ2 (OR = 5.1, P = 0.03). In women with RPL the three mutations did not show any significant association, levels of Protein C, protein S and PCAT-NR in patient groups not different from controls (P > 0.05). In conclusion, we recommend expanding on these data to provide larger-scale studies.

Objectives: Central retinal vein occlusion (CRVO) is a severe eye disease that impairs vision. Although numerous systemic conditions have been reported to be a contributor, its exact pathophysiology has not yet been resolved. The purpose of this study was to study the role of some common thrombophilic polymorphisms in CRVO patients. Methods: A total of 33 CRVO patients (25 non-ischemic CRVO and 8 ischemic CRVO) and 30 controls were recruited. Factor V Leiden (G1691A), prothrombin (Factor II G20210A), MTHFR (C677T), MTHFR (A1298C), and PAI-1 5G/4G polymorphisms in venous blood DNA samples were examined, as well as the presence of hypertension, diabetes mellitus, glaucoma, smoking, and history of thrombosis. Results: It was determined that MTHFR C677T polymorphisms, either in heterozygous or homozygous form, might be a risk factor for CRVO and systemic thrombosis. No differences were detected between the CRVO and control groups in terms of diabetes mellitus (p=0.058>0.05), hypertension (p=0.3>0.05), smoking (p=0.923>0.05), glaucoma (p=0.06>0.05) or use of anticoagulant drugs (p=0.4>0.05). Analysis of patient history revealed a statistically significant difference regarding a thrombotic event in the medical history of the CRVO group (p=0.001<0.05; n=4) versus the control group. The ischemic CRVO group had a significantly higher incidence of diabetes mellitus (p=0.002<0.05) and hypertension (p=0.031<0.05) than the non-ischemic CRVO group. Conclusion: The MTHFR C677T mutation appears to be a risk factor for CRVO but factor V Leiden (G1691A), prothrombin (Factor II G20210A), MTHFR (A1298C), and PAI-1 5G/4G mutations were not determined to be specifically related to CRVO in this study. The presence of diabetes mellitus and hypertension was significant in the ischemic CRVO group. Further studies with larger sample sizes should be conducted. [ABSTRACT FROM AUTHOR]