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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 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]

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 < 0.001*). On the other hand, no significant difference (P = 0.143) in the expression level of TYMS was found. Gene expression of DNMT3B was upregulated by 1.65-fold in all breast cancerous tissue samples compared with the control normal adjacent tissue with mean ± SD of 1.81 ± 0.63. (P ≤ 0.001*). Conclusion: The current study showed that the 2R/3R TYMS allele and DNMT3B (− 149C>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. [ABSTRACT FROM AUTHOR]

Cardiovascular disorders (CVD) broadly include coronary heart disease, stroke, congenital heart disease, peripheral artery disease, deep vein thrombosis, and other less common conditions. The risk factors for arterial thrombosis are usually divided into those that are modifiable and nonmodifiable. Herein, we aimed to characterize a cohort of arterial thrombosis patients from the Georgian Adjarian population. In this study, 89 arterial thrombosis patients (male=71.3%, female=28.7%)were enrolled. Patients' mean age was 66.3± 12.1 years. Troponin levels from the venous blood from patients and computed tomography (CT) assessments were used for myocardial infarction (MI) and ischemic stroke diagnosis. The venous blood from arterial thrombosis patients were used for polymerase chain reaction (PCR). PCR was performed to determine the presence of three genetic markers of thrombosis risk, viz., factor V Leiden (FVL) G1691A, prothrombin (PT) G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms. In all, 83% of cases were diagnosed with MI and 13% with ischemic stroke. Also, 22.5% of the patients had diabetes, 73% hypertension, 49.3% had a family history of thrombosis, 34.8% consumed alcohol regularly (all males), and 63.4% of cases were smokers. The frequency of the FVL allele polymorphism in our cohort was 2.25%, which corresponded to a heterozygous frequency of 4.5%. The frequency of heterozygosity for the PT G20210A polymorphism was 2.25%; while the frequency of the MTHFR C677T allele polymorphism was 31.46%, which corresponded to heterozygous and homozygous stage frequencies of 51.7% and 5.6%, respectively. In conclusion, we described the first cohort of arterial thrombosis patients in the Georgian Adjarian population, and the description of the clinical and molecular characteristics of patients with arterial thrombosis thus obtained may be useful to researchers, healthcare professionals, and policy makers while making decisions regarding the prevention, treatment, and follow-up of such patients. [ABSTRACT FROM AUTHOR]