Comparison of MED 12 gene mutation and microRNA-124 expression in leiomyoma and myometrium of Turkish patients.

OBJECTIVES: It is believed that there are still unclear areas in the formation mechanism of leiomyomas. In our study, it was aimed to investigate the formation mechanisms of leiomyomas due to local MED 12 gene exon 2 mutation and local microRNA-124 expression in a Turkish population. MATERIAL AND METHODS: Thirty patients who underwent hysterectomy for leiomyoma uteri at Gaziantep University between January 2013 and January 2016 were included in our study. In the pathology specimens of these patients, the patient's myometrium tissue and her own leiomyoma tissue were analysed via quantitative Realtime PCR in association with MED 12 exon 2 mutation and microRNA-124 expression. RESULTS: The average age of the 30 patients included in our study is 46.67 ± 5.42 and 13 patients had single leiomyoma; 17 patients had more than one leiomyoma. There were significantly higher c.130G> T (p.G44C) mutation and c.131G> A (p.G44A) mutation of MED 12 gene exon in leiomyoma tissues than healthy myometrium tissues of same patients. There was a 3.7-fold decrease in the expression of microRNA-124 in leiomyoma tissues compared to intact eutopic myometrium tissues, but this difference was not statistically significant. CONCLUSIONS: In recent studies, it has been suggested that MED 12 gene may play an active role in the formation of fibroids. MED12 and ß-catenin / Wnt pathway were emphasized, and alternative genetic pathways are sought in fibroid formation. Also, tumour suppressor and oncogenesis effects of microRNAs have been demonstrated in many different studies. Since it is involved in the Wnt pathway, microRNA-124 has been blamed by some previous studies for the formation of fibroids. This study demonstrates that MED12 exon 2 mutations and probably microRNA-124 gene expressions might contribute to uterine leiomyoma pathology.

Transcriptomic analysis of asymptomatic and symptomatic severe Turkish patients in SARS-CoV-2 infection.

Objective: Coronavirus disease 2019 (COVID-19), leading to mild infection (MI), acute respiratory distress syndrome or death in different persons. Although the basis of these variabilities has not been fully elucidated, some possible findings have been encountered. In the present study, we aimed to reveal genes with different expression profiles by next-generation sequencing of RNA isolated from blood taken from infected patients to reveal molecular causes of different response. Methods: Two healthy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative control individuals (NCI), two SARS-CoV-2-positive patients who have MI, and two patients who have critical infection (CI) were included in the study. Total RNA was extracted from blood samples and sequenced. Raw RNA-Seq data were analyzed on Galaxy platform for the identification of differentially expressed genes and their pathway involvements. Results: We found that 199 and 521 genes were downregulated in whole blood of COVID-19-positive CI patients compared to NCI and MI patients, respectively. We identified 21 gene ontology pathways commonly downregulated in CI patients compared to both NCI and MI, mostly associated with innate and adaptive immune responses. Three hundred and fifty-four and 600 genes were found to be upregulated compared to NCI and MI, respectively. Upregulated six pathways included genes that function in inflammatory response and inflammatory cytokine release. Conclusion: The transcriptional profile of CI patients deviates more significantly from that of MI in terms of the number of differentially expressed genes, implying that genotypic differences may account for the severity of SARS-CoV-2 infection and inflammatory responses through differential regulation of gene expression. Therefore, further studies that involve whole genome analysis coupled with differential expression analysis are required in order to determine the dynamics of genotype - gene expression profile associations.

Investigation of Scavenger Receptor Class B Type I gene variants in patients with coronary heart disease with a history of early myocardial infarction.

OBJECTIVE: The scavenger receptor class B type 1 (SR-BI, SCARB1), which is a high-density lipoprotein (HDL) receptor that mediates selective cholesteryl ester uptake, plays an important role in reverse cholesterol transport. This study investigated the distribution of polymorphic variants of the SR-BI gene in patients with coronary heart disease (CHD) with a history of early myocardial infarction (MI) at an early age and their effects on their serum lipid levels. METHODS: SR-BI rs5888(T>C), rs4238001(C>T), and rs10846744(G>C) were analyzed in 100 male patients with CHD with a history of MI (MI+) who were younger than 50 years and 89 male control subjects without MI history (MI-) using real-time polymerase chain reaction (PCR) and mutant-allele-specific PCR techniques. RESULTS: SR-BI rs4238001 common-CC genotype was found to be more frequent in patients with MI+ than in control subjects (MI-; odds ratio 4.046, p<0.001). The rs10846744 rare-C allele showed a significant association with increased total cholesterol (p=0.014) and triglyceride (p=0.009) levels in the MI+ CHD group. Logistic regression analysis confirmed that there may be an association between the rs4238001-CC genotype (p=0.002), smoking (p=0.026), and MI+ CHD in the presence of other risk factors associated with CHD, whereas haplotype analysis confirmed that patients with MI+ CHD (rs5888-C, rs10846744-G, and rs4238001-C alleles) and CCC (rs5888-C, rs10846744-C, and rs4238001-C alleles) haplotypes were highly frequent (p<0.01 and p=0.027, respectively). CONCLUSION: These results indicated that SR-BI gene variants show different distribution in patients with MI+ CHD compared with that in MI- control subjects, and these variants may have effects in favor of dyslipidemia.

Vitamin D Levels of Outpatients Admitted to a University Hospital in the Marmara Region of Turkey Over 3 Years.

BACKGROUND: Vitamin D regulates calcium and phosphorus metabolism, and it is essential for bone formation. Several factors can affect vitamin D levels in plasma. In present study we compare vitamin D levels of outpatients, who admit to Maltepe University Hospital between 2011 and 2013 and had vitamin D measurements regarding gender, age, and season. METHODS: Hospital records were evaluated to identify the outpatients with vitamin D levels and their gender, age, and vitamin D levels and the seasons of measurements were recorded. RESULTS: Data of 4860 subjects (74% female) were analyzed and 69.2% were between 18-64 years old. Vitamin D levels were as follows: 43.1% ≤ 10 ng/mL, 31.9% between 10 ng/mL and 20 ng/mL, 16.1% between 20 ng/mL and 30 ng/mL, and only 8.9% ≥ 30 ng/mL. The number of females with vitamin D levels < 10 ng/mL was significantly higher than that of males, while the number of males with vitamin D levels between 10 ng/mL and 20 ng/mL was significantly higher than that of females (P = 0.001) for each of the individuals, 6.2% and 11.1% had sufficient levels in winter and summer, respectively. Overall, it was observed that 6.6% of individuals between 18-44 years old, 8.2% of individuals between 45-64 years old and 10.3% of individuals over 65 years old had vitamin D levels > 30 ng/mL. CONCLUSIONS: The prevalence of vitamin D deficiency in outpatients of Maltepe University Hospital in Marmara region was 75% (< 20 ng/mL).

Investigation of JAM-A (rs790056) and LFA-1 (rs8058823) gene variants in Turkish colorectal cancer patients.

BACKGROUND/AIMS: Lymphocyte function-associated antigen 1 (LFA-1) is a transmembrane glycoprotein expressed on the surface of leukocytes and containing the binding domain for junctional adhesion molecule-A (JAM-A). The aim of the present study was to evaluate the effects of JAM-A and LFA-1 variants on the formation of colorectal cancer and metastasis. MATERIALS AND METHODS: A total of 82 subjects with colorectal cancer and 67 healthy subjects were studied. DNA was isolated from blood samples, and variations were determined using the polymerase chain reaction and restriction fragment length polymorphism method. RESULTS: JAM-A rs790056 CC genotype and C allele were found to be higher in the colorectal cancer group (p<0.05), and approximately 3-fold increased colorectal cancer risk with CC genotype was determined (p=0.029). Haplotype analysis showed that GC haplotype (LFA-1 rs8058823G and JAM-A rs790056C) frequency was significantly higher in the patient group (p=0.041) than in controls. CONCLUSION: JAM-A rs790056 variation may be effective in the development of colorectal cancer.

Association between PTEN IVS4 polymorphism and development of colorectal cancer in a Turkish population.

BACKGROUND: Phosphatase and tensin homolog (PTEN) is one of the most frequently mutated suppressor genes in human cancers. However, there are no data about the role of PTEN IVS4 polymorphism in development of colorectal cancer (CRC). The authors aimed to determine the role of PTEN IVS4 variants in the etiology of CRC. PATIENTS AND METHODS: A hospital-based case-control study was conducted in 203 patients with CRC (127 colon, 76 rectum) and 245 healthy controls. The frequencies of PTEN IVS4 (rs 3830675) genotypes were determined by using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: The (-/-) genotype of PTEN IVS4 that absence of ATCTT insertion at downstream of exon 4 in intron 4 of PTEN gene was found to be associated with 1.55-fold increased risk of colon cancer (p < 0.005; OR: 1.55, 95% CI: 1.24 - 1.94) and 1.4-fold increased risk of rectum cancer (p < 0.005; OR: 1.4, 95% CI: 1.08 - 1.82). Subgroup analyses showed that PTEN IVS4 genotypes were not associated with any clinicopathological characteristics of patients with CRC (p > 0.05). CONCLUSION: The (-/-) genotype of PTEN IVS4 gene might be associated with increased risk for development of CRC in a Turkish population. Further studies will clarify the exact role of PTEN IVS4 polymorphism in the etiology of CRC.

Increased gastric cancer risk with PTEN IVS4 polymorphism in a Turkish population.

We aimed to investigate the association of the phosphatase and tensin homolog (PTEN) IVS4 polymorphism with a gastric cancer (GC) risk in the Turkish population. A hospital-based case-control study was conducted in 93 patients with GC, and 113 healthy controls. The PTEN IVS4 (rs no: 3830675) polymorphism was determined by using polymerase chain reaction-restriction fragment length polymorphism analysis. The PTEN IVS4 (-/-) genotype exhibited a significantly elevated risk for GC compared to controls (p<0.005; odds ratio: 1.6, 95% confidence interval: 1.19-2.14). Analyses on clinicopathological parameters showed that PTEN IVS4 genotypes were not associated with any of the variables of patients with GC (p>0.05). In conclusion, the PTEN IVS4 polymorphism might contribute to the development of GC in a Turkish population. Further studies, including comparison of the PTEN IVS4 polymorphism with plasma and tissue expressions of PTEN in larger study size groups will provide a further assessment of the PTEN IVS4 polymorphism in GC patients.