Determination of the Relationship Between DNA Methylation Status of KLOTHO and ARNTL Genes With Hypertension.

Hypertension is a multifactorial chronic disease due to the interaction of environmental factors with genetic alteration. KLOTHO and ARNTL genes play an important role in the development of hypertension. Therefore, we analyzed the methylation status of KLOTHO and ARNTL genes by using methylation-sensitive high-resolution melting (MSHRM) in a total of 78 hypertensive and 49 control subjects. In this study, we could not identify a significant association between KLOTHO and ARNTL methylation and the hypertensive phenotype. Moreover, we could not find a direct association between KLOTHO and ARNTL methylation and the fasting blood sugar, triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, sodium (Na), creatinine (Cr), potassium (K), and urea levels in hypertensive patients. However, we found a significant difference between the methylated KLOTHO hypertensive patients and the unmethylated KLOTHO control subjects for potassium (K).

RANKL is a new Epigenetic Biomarker for the Vasomotor Symptom During Menopause.

During menopausal transition, decreased level of estrogen brings a number of physiological problems and hormonal changes. In this study, promoter methylation of RANKL and FSHR genes were identified in 30 premenopausal and 35 postmenopausal women using methylation-specific high resolution melting (MS-HRM) analysis. The statistical analyses and their association with patient characteristics were performed by Pearson χ2 and Fisher's exact test (p <0.05). The methylated RANKL gene was detected in 16 postmenopausal cases, and 12 (75.0%) of the RANKL methylated cases had hot flashes (p = 0.024). The methylated FSHR gene was detected in 18 postmenopausal cases, and 13 (75.0%) of the methylated cases had hot flashes (p = 0.028). In vitro studies demonstrated the association between RANKL expression, FSH level and hot flashes in the mouse. Although lack of epigenetic studies in this field proves our results crucial and therefore, our results showed magnitude of epigenetic profiles of Turkish Cypriot post-menopausal women. This was the first study which has investigated the RANKL and FSHR methylation and their relationship with hot flashes in postmenopausal women.

Do We Use Methylation of NFATC1 and FOS Genes As a Biomarker for Postmenopausal Osteoporosis?

Genetic and epigenetic factors have an important role during the development of osteoporosis. Receptor activator of nuclear factor-κ B (NF-κB) (RANK)/receptor activator of NF-κB ligand (RANKL) pathway is important for the bone remodeling, and NFATC1 and FOS are the downtargets of this pathway. Here, we report methylation status of NFATC1 and FOS genes in post- and premenopausal women. In this study, 30 premenopausal and 35 postmenopausal women were included. Methylation sensitive-high resolution melting (MS-HRM) analysis was used for identification of NFATC1 and FOS genes methylation. The NFATC1 gene was methylated in 11 of the 35 postmenopausal women, and the FOS gene was methylated in six of the postmenopausal women (p >0.005). Here, we found statistically significant association between unmethylation of the NFATC1 gene and postmenopausal status. This result explains the epigenetic regulation of osteoclasts during the menopausal transition, and for the first time, our results can be used for epigenetic explanation of postmenopausal osteoporosis in the literature. However, the limited number of studies in this field makes our results crucial. Our results showed great value of epigenetic profiles of postmenopausal women.

Pros and Cons for Fluorescent in Situ Hybridization, Karyotyping and Next Generation Sequencing for Diagnosis and Follow-up of Multiple Myeloma.

Multiple myeloma (MM) is one of the plasma cell-related hematological malignancies exceeding 10.0% of all marrow cells, and they make a paraprotein that is a marker of the disease. Myeloma is one of the most common types of hematological malignancies in humans. Genetic bio-markers have been used for prognostic markers in patients diagnosed with MM. The genetic and genomic changes have been identified using karyotyping, fluorescent in situ hybridization (FISH), next generation sequencing (NGS), specifically whole-genome sequencing or exome sequencing. Circulatory plasma cells, circulating free DNA (cfD-NA) and microRNAs (miRNAs) comprised in liquid biopsy are potentially used in diagnosis/prognosis of MM. In this study, we analyzed and compared results of karyo-typing, FISH and NGS in 35 MM cases. Diagnostic strategies are expanding rapidly and newly developed NGS-based testing may help the understanding of the complexities of genetic alterations in karyotypically normal cases.