Contribution of genotypes in Prothrombin and Factor V Leiden to COVID-19 and disease severity in patients at high risk for hereditary thrombophilia.

Thrombotic and microangiopathic effects have been reported in COVID-19 patients. This study examined the contribution of the hereditary thrombophilia factors Prothrombin (FII) and Factor V Leiden (FVL) genotypes to the severity of COVID-19 disease and the development of thrombosis. This study investigated FII and FVL alleles in a cohort of 9508 patients (2606 male and 6902 female) with thrombophilia. It was observed that 930 of these patients had been infected by SARS-CoV-2 causing COVID-19. The demographic characteristics of the patients and their COVID-19 medical history were recorded. Detailed clinical manifestations were analyzed in a group of cases (n = 4092). This subgroup was age and gender-matched. FII and FVL frequency data of healthy populations without thrombophilia risk were obtained from Bursa Uludag University Medical Genetic Department's Exome Databank. The ratio of males (31.08%; 27.01%) and the mean age (36.85 ± 15.20; 33.89 ± 14.14) were higher among COVID-19 patients compared to non-COVID-19 patients. The prevalence of FVL and computerized tomography (CT) positivity in COVID-19 patients was statistically significant in the thrombotic subgroup (p < 0.05). FVL prevalence, CT positivity rate, history of thrombosis, and pulmonary thromboembolism complication were found to be higher in deceased COVID-19 patients (p < 0.05). Disease severity was mainly affected by FVL and not related to genotypes at the Prothrombin mutations. Overall, disease severity and development of thrombosis in COVID-19 are mainly affected by the variation within the FVL gene. Possible FVL mutation should be investigated in COVID-19 patients and appropriate treatment should be started earlier in FVL-positive patients.

The relationship between KRAS LCS6 polymorphism and endometrium cancer.

The aim of this study was to investigate the relationship between KRAS LCS6 mutation and endometrial cancer (EC). The study included 105 patients who had hysterectomy for benign reasons and 99 EC patients. The patients with Type 1 EC were classified according to histological properties, cancer stage, grade, tumour dimension, myometrial invasion (MMI), lymphovascular invasion (LVI), cytology, and number of positive lymph nodes. KRAS LCS6 mutation was examined in blood samples taken from all patients in both groups. No statistically significant difference was determined between the EC patients and the control group in demographic features. Weight and the Body Mass Index (BMI) values were higher in EC group (p < .001). While the incidence of this polymorphism is 5.8% throughout the world, the polymorphism rate was found to be 16.2% in the EC group and 12.4% in the control group, with no statistically significant difference determined (p > .05). Despite the higher rate of LCS6 polymorphism incidence in EC patients in this study conducted on a relatively large sample, there was not found to be a statistically significant difference in comparison with the control group. In addition, the presence of LCS6 polymorphism was not determined to have an effect on EC histopathological characteristics.Impact statementWhat is already known on this subject? Endometrial cancer (EC) is a genital system cancer which is one of the most widespread gynecological cancers seen in the USA and other developed countries, In EC, the most frequently seen gene mutations are PTEN tumour suppressor gene, KRAS, ß1 catenin, BCL-2, CTNNB and P53 mutations. KRAS LCS6(let-7 miRNA binding region polymorphism) polymorphism has a worldwide incidence of 5.8% (Chin et al. 2008).There are studies shown that KRAS LCS6 polymorphism has an effect on developing EC (Lee et al. 2014), ovarian cancer(Ratner et al. 2010)and endometriosis in women (Grechukhina et al. 2012).What do the results of this study add? In our study, LCS6 located on KRAS 3'-UTR was found at the rate of 16.2% in Type 1 EC patients. This increase is noticeable when it is considered that the incidence of this polymorphism is 5.8% in the general population. The results of the current study supports the preliminary findings of Lee et al.What are the implications of these findings for clinical practice and/or further research? These new genetic markers could help to develop gene-targeted therapies, identify genetic basis of the disease and the factors that could affect the EC prognosis.

Vitamin D can be used as a supplement against cancer stem cells.

Cancer is standing like a bottomless pit or a black hole in front of mankind. Scientists are trying all possible ways to find a solution against to cancer. As known, cancer is a phenomenon fed from internal dynamics. One of internal dynamic is cancer stem cells that are involved in the formation and development of cancer. Because of these dynamics, scientists began to search solution inside of the body. Another internal dynamic is vitamin D and it is not only important in calcium homeostasis but also it is important for cell proliferation, differentiation, and apoptosis. In this study, we investigated the effect of vitamin D on cancer stem cells that sorted from MCF-7 cell line and on HEK293 cell line as control. Our results showed that calcitriol treatment reduced the number of CSC (Cancer Stem Cell) in the MCF-7 cell while increased in HEK293 cell population. Gene expression analyses showed that effect of calcitriol on apoptosis plays an important role in this reduction. Deficiency or unavailability of vitamin D may take a role in the pathogenesis of breast cancer.

Follicle-stimulating hormone receptor gene polymorphisms in women with endometriosis.

OBJECTIVES: The purpose of this study was to evaluate the influence of the follicle-stimulating hormone (FSH) receptor poymorphisms Asn680Ser and Thr307Ala on endometriosis in Turkish women. METHODS: Polymorphic analysis of the FSH receptor gene was performed in 100 patients with endometriosis and 100 controls. Genomic DNA was obtained from peripheral blood leukocytes and polymorphisms were investigated using restriction fragment length polymorphism analysis. RESULTS: There were no significant differences in genotype frequencies of FSH receptor gene between endometriosis patients and controls. When the patients were divided into two groups according to disease severity, we found that the patients with the SS (680 Ser/Ser) or AA (307 Ala/Ala) genotype were less likely to develop stage 3-4 endometriosis compared to the stage 1-2 endometriosis group (P = 0.004; OR: 0.177, 95% CI 0.055-0.568 and P = 0.040; OR: 0.240, 95% CI 0.061-0.938; respectively). CONCLUSIONS: The distributions of FSHR polymorphisms may not have an effect on endometriosis development but they are associated with the severity of the disease. The polymorphisms encoding SS at the position 680 and AA at the position 307 and the patients with the genotype that included alanine or serine were less likely to develop stage 3-4 endometriosis compared to the stage 1-2 endometriosis group.

PAX9 polymorphisms and susceptibility with sporadic tooth agenesis in Turkish populations: a case-control study.

BACKGROUND: Hypodontia, the congenital absence of one or a few teeth is one of the most common alterations of the human dentition. Familial hypodontia is caused by mutations in PAX9, Msx1 and Axin2 genes. Limited numbers of studies are present to show etiological factors beyond this anomaly in Turkish community belonging to Caucasian racial family. The purpose of this study is to investigate the relationships between the two different single nucleotide polymorphisms that are G-1031A and T-912C with hypodontia in Caucasians. 200 individuals having hypodontia and 114 normal individuals having all 32 teeth present were selected for the study. Blood samples were collected from each individual and DNA was extracted. To determine the polymorphisms, PCR-RFLP method was used. RESULTS: The outcomes suggest that the individuals having AC haplotype carry less risk in having hypodontia compared with the rest of the haplotype groups (OR = 3.88; CI = 95%; p = 0.001). The ratio of GT haplotype is less in the hypodontia group meaning that the GT carriers are in risk group in terms of hypodontia risk. CONCLUSION: These results indicate that polymorphisms in the promoter region of PAX9 gene may have an influence on the transcriptional factors and activity of this gene and are associated with hypodontia in Caucasian individuals.

Investigation of oxidative stress markers in essential hypertension.

BACKGROUND: The main goal of this study was to evaluate ischemia modified albumin (IMA), total antioxidant status (TAS), and total oxidant status (TOS) levels in treated essential hypertensive patients and to compare them with levels of normotensive subjects. METHODS: In 45 hypertensive and 30 control subjects, serum levels of IMA were determined manually using a spectrophotometric Co(II)-albumin binding assay. TAS and TOS levels were evaluated spectrophotometrically. Lipid profile was estimated by routine methods. RESULTS: Hypertensive patients had significantly higher levels of TOS and IMA (p = 0.020 and p = 0.034, respectively) and lower levels of TAS (p = 0.016) in comparison with control subjects. Serum levels of TAS were negatively correlated with TOS and IMA levels in the patient group. Serum levels of TOS were also positively correlated with IMA levels. There was no significant correlation between blood pressure and TAS, TOS, and IMA levels. CONCLUSIONS: Our results showed higher levels of IMA in hypertensive patients. We suggest that higher levels of IMA may result from increased oxidative stress and decreased antioxidant status in hypertensive patients.