Do we use methylation of NFATC1 and FOS genes as a biomarker for postmenopausal osteoporosis?

Abstract 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.

Download Full-text

Does methylation of NFATC1 and C-FOS genes are associated with post-menopausal osteoporosis?

10.1101/2020.02.19.955682 ◽

2020 ◽

Author(s):

Rasime Kalkan ◽

Özgür Tosun

Keyword(s):

Postmenopausal Women ◽

Epigenetic Regulation ◽

Methylation Status ◽

Menopausal Status ◽

Epigenetic Factors ◽

Post Menopausal Osteoporosis ◽

Menopausal Women ◽

Post Menopausal ◽

First Time ◽

Menopausal Osteoporosis

ABSTRACTGenetic and epigenetic factors have an important role during the development of osteoporosis. RANK/RANKL pathway is important for the bone remodeling and NFATC1 and c-FOS are the downtargets of this pathway. Here, we report methylation status of NFATC1 and C-FOS genes in post and premenopausal cases. In this study 30 pre-menopausal and 35 post-menopausal cases were included. MS-HRM was used for identification of NFATC1 and C-FOS metyhylation.NFATC1 were methylated in 11 of the 35 post-menopausal women and C-FOS were methylated in 6 of the postmenopausal women (p >0.005). Here, we found statistically significant association between unmethylation of NFATC1 and post-menopausal status. This result explains the epigenetic regulation of osteoclasts during the menopausal transition and our results can be used for epigenetic explanation of post-menopausal osteoporosis for the first time in the literature. Although the limited number of studies in this field makes our results crucial. Therefore, our results showed great value of epigenetic profile of post-menopausal women.

Download Full-text

Plasma Levels of Protein S, Protein C, and Factor X: Effects of Sex, Hormonal State and Age

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649925 ◽

1995 ◽

Vol 74 (05) ◽

pp. 1271-1275 ◽

Cited By ~ 36

Author(s):

C M A Henkens ◽

V J J Bom ◽

W van der Schaaf ◽

P M Pelsma ◽

C Th Smit Sibinga ◽

...

Keyword(s):

Regression Analysis ◽

Postmenopausal Women ◽

Protein C ◽

Blood Donors ◽

Premenopausal Women ◽

Protein S ◽

The Other ◽

Factor X ◽

Normal Ranges

SummaryWe measured total and free protein S (PS), protein C (PC) and factor X (FX) in 393 healthy blood donors to assess differences in relation to sex, hormonal state and age. All measured proteins were lower in women as compared to men, as were levels in premenopausal women as compared to postmenopausal women. Multiple regression analysis showed that both age and subgroup (men, pre- and postmenopausal women) were of significance for the levels of total and free PS and PC, the subgroup effect being caused by the differences between the premenopausal women and the other groups. This indicates a role of sex-hormones, most likely estrogens, in the regulation of levels of pro- and anticoagulant factors under physiologic conditions. These differences should be taken into account in daily clinical practice and may necessitate different normal ranges for men, pre- and postmenopausal women.

Download Full-text

Copper-Induced Epigenetic Changes Shape the Clinical Phenotype in Wilson Disease

Current Medicinal Chemistry ◽

10.2174/0929867327666200730214757 ◽

2020 ◽

Vol 27 ◽

Author(s):

Daniela Fanni ◽

Clara Gerosa ◽

Valeria Marina Nurchi ◽

Rosita Cappai ◽

Marta Mureddu ◽

...

Keyword(s):

Wilson Disease ◽

Clinical Presentation ◽

Clinical Phenotype ◽

Methylation Status ◽

Copper Metabolism ◽

Epigenetic Factors ◽

Genetic Changes ◽

Illness Onset ◽

Phenotypic Manifestation ◽

Copper Overload

: Wilson disease is a congenital disorder of copper metabolism whose pathogenesis remains, al least in part, unknown. Subjects carrying the same genotype may show completely different phenotypes, differing for the age at illness onset or for the hepatic, neurologic or psychiatric clinical presentation. The inhability to find a unequivocal correlation between the type of mutation in the ATPase copper transporting beta (ATP7B) gene and the phenotypic manifestation, induced many authors to look for epigenetic factors interacting with the genetic changes. Here the evidences regarding the ability of copper overload to change the global DNA methylation status are discussed.

Download Full-text

Exogenous female sex steroid hormones and risk of asthma and asthma-like symptoms: a cross sectional study of the general population

Thorax ◽

10.1136/thx.56.8.613 ◽

2001 ◽

Vol 56 (8) ◽

pp. 613-616

Author(s):

P Lange ◽

J Parner ◽

E Prescott ◽

C Suppli Ulrik ◽

J Vestbo

Keyword(s):

General Population ◽

Postmenopausal Women ◽

Hormone Replacement ◽

Premenopausal Women ◽

Cross Sectional Study ◽

Asthma Medication ◽

Hormonal Contraceptives ◽

Cross Sectional ◽

Heart Study ◽

Prescription Practice

BACKGROUNDRecent evidence suggests a role for hormonal factors in the aetiology of asthma.METHODSData from a large study of women selected from the general population were used to relate treatment with oral hormonal contraceptives (OCP) and postmenopausal hormone replacement therapy (HRT) to the following asthma indicators: self-reported asthma, wheezing, cough at exertion, and use of medication for asthma. The study sample comprised 1536 premenopausal and 3016 postmenopausal women who participated in the third round of the Copenhagen City Heart Study in 1991–4. A total of 377 women were taking OCP (24.5% of premenopausal women) and 458 were on HRT (15.2% of postmenopausal women).RESULTSIn premenopausal women 4.8% reported having asthma. The prevalence of self-reported asthma, wheeze, use of asthma medication, and cough at exertion was not significantly related to use of OCP. In postmenopausal women the prevalence of self-reported asthma was 6.2%. A weak but consistent association was observed between HRT and self-reported asthma (OR 1.42 (95% CI 0.95 to 2.12)), wheeze (OR 1.29 (95% CI 1.02 to 1.64)), cough at exertion (OR 1.34 (95% CI 1.01 to 1.77)), and use of asthma medication (OR 1.45 (95% CI 0.97 to 2.18)).CONCLUSIONSIn this study of the general population no relationship was found between the use of OCP and asthma. Although an association was observed between HRT and asthma and asthma-like symptoms, this was relatively weak and it is concluded that there is no necessity to change present prescription practice.

Download Full-text

POS0841 RISK FACTORS OF LOW BONE MINERAL DENSITY IN WOMEN WITH SYSTEMIC SCLEROSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1339 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 674.2-675

Author(s):

A. Efremova ◽

N. Toroptsova ◽

N. Demin ◽

O. Dobrovolskaya ◽

O. Nikitinskaya

Keyword(s):

Risk Factors ◽

Bone Mineral Density ◽

Systemic Sclerosis ◽

Postmenopausal Women ◽

Bone Mineral ◽

Cumulative Dose ◽

Premenopausal Women ◽

C Reactive Protein ◽

Mineral Density ◽

Reactive Protein

Background:Chronic inflammatory rheumatic diseases are risk factors of bone loss and fractures. Systemic sclerosis (SSc) has been recognized to be another potential inflammatory joint disease that may affect bone tissue.Objectives:to evaluate bone mineral density (BMD) and risk factors of low BMD in women with SSc.Methods:173 women, among them 110 postmenopausal (median age 60[55,63] years) and 63 premenopausal (median age 35[31,44] years). BMD was measured at lumbar spine (LS), femoral neck (FN) and total hip (TH) by dual energy X-ray absorptiometry (DXA, Hologic 4500A). Low BMD was diagnosed if the T-score was < -1.0 standard deviation (SD) in postmenopausal women and if the Z-score was < -2.0 SD in premenopausal women. The relationship between BMD and SSc patients’ characteristics was evaluated using univariate linear regression analysis.Results:Low BMD was found in 66% patients: 79% - in postmenopausal and 18% - in premenopausal women. Among postmenopausal persons osteoporosis was discovered in 47% and osteopenia – in 32% cases. In postmenopausal woman BMD of LS, FN and TH were associated with body mass index (BMI) (β=0.27, p=0.010; β=0.47, p<0,001 and β=0.45, p<0,001, respectively), duration of glucocorticoids (GCs) using (β=-0.31, p=0.008; β=-0.34, p=0.003 and β=-0.27, p=0.022, respectively); BMD of FN and TH with C-reactive protein (β= -0.32, p=0.016 and β= -0.29, p=0.029, respectively) and LS BMD with current and cumulative GCs dose (β= -0.24, p=0.039 and β= -0.29, p=0.014, respectively). In premenopausal women BMD of LS, FN and TH were associated with BMI (β=0.51, p<0,001; β=0.45, p=0.003 and β=0.47, p=0.002, respectively), duration of GCs using (β= -0.45, p=0.004; β= -0.47, p=0.003 and β= -0.48, p=0.002, respectively) and GCs cumulative dose (β= -0.48, p=0.002; β= -0.51, p=0.001 and β= -0.46, p=0.004, respectively); BMD of FN and TH with 25(ОН)D level (β=0.52, p=0.008 and β=0.54, p=0.005, respectively), and LS BMD with SSc duration (β= -0.44, p=0.004).Conclusion:Low BMD was diagnosed in 66% of women with SSc. Low BMI, GCs cumulative dose and duration of GCs using were independent risk factors for low BMD in both premenopausal and postmenopausal persons. Additional factors as SSc duration and low vitamin D level were found out for premenopausal and current GCs dose and C-reactive protein level for postmenopausal women.Disclosure of Interests:None declared

Download Full-text

Mammographic microcalcifications and risk of breast cancer

British Journal of Cancer ◽

10.1038/s41416-021-01459-x ◽

2021 ◽

Author(s):

Shadi Azam ◽

Mikael Eriksson ◽

Arvid Sjölander ◽

Marike Gabrielson ◽

Roxanna Hellgren ◽

...

Keyword(s):

Breast Cancer ◽

Postmenopausal Women ◽

Detection System ◽

Premenopausal Women ◽

Computer Aided Detection ◽

Comprehensive Information ◽

Estimated Risk ◽

Logistic Regressions ◽

Microcalcification Clusters

Abstract Background Mammographic microcalcifications are considered early signs of breast cancer (BC). We examined the association between microcalcification clusters and the risk of overall and subtype-specific BC. Furthermore, we studied how mammographic density (MD) influences the association between microcalcification clusters and BC risk. Methods We used a prospective cohort (n = 53,273) of Swedish women with comprehensive information on BC risk factors and mammograms. The total number of microcalcification clusters and MD were measured using a computer-aided detection system and the STRATUS method, respectively. Cox regressions and logistic regressions were used to analyse the data. Results Overall, 676 women were diagnosed with BC. Women with ≥3 microcalcification clusters had a hazard ratio [HR] of 2.17 (95% confidence interval [CI] = 1.57–3.01) compared to women with no clusters. The estimated risk was more pronounced in premenopausal women (HR = 2.93; 95% CI = 1.67–5.16). For postmenopausal women, microcalcification clusters and MD had a similar influence on BC risk. No interaction was observed between microcalcification clusters and MD. Microcalcification clusters were significantly associated with in situ breast cancer (odds ratio: 2.03; 95% CI = 1.13–3.63). Conclusions Microcalcification clusters are an independent risk factor for BC, with a higher estimated risk in premenopausal women. In postmenopausal women, microcalcification clusters have a similar association with BC as baseline MD.

Download Full-text

Association between Soy Food and Dietary Soy Isoflavone Intake and the Risk of Cardiovascular Disease in Women: A Prospective Cohort Study in Korea

Nutrients ◽

10.3390/nu13051407 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1407

Author(s):

Jihyun Im ◽

Kyong Park

Keyword(s):

Cardiovascular Disease ◽

Postmenopausal Women ◽

Premenopausal Women ◽

Soy Isoflavones ◽

Korean Women ◽

Cvd Risk ◽

Soy Isoflavone ◽

Soy Foods ◽

Cardiovascular Disease In Women

The association between soy food and soy isoflavone intake and cardiovascular disease (CVD) risk is uncertain, especially in women. We aimed to investigate this association in Korean women. We analyzed data from the Korean Genome and Epidemiology Study, including 4713 Korean women aged 40–69 years with no CVD or cancer at baseline. Dietary information was obtained using a validated semi-quantitative food frequency questionnaire, and the incidence of CVD was assessed using biennial self-reported questionnaires on medical history. The mean follow-up time was 7.4 years, during which 82 premenopausal and 200 postmenopausal women reported CVD incidence. The highest tofu, total soy foods, and dietary soy isoflavone intake groups were significantly associated with a decreased CVD risk in premenopausal women (tofu: hazard ratio (HR) 0.39; 95% confidence interval (CI), 0.19–0.80; total soy food: HR 0.36; 95% CI, 0.18–0.70; dietary soy isoflavones: HR 0.44; 95% CI, 0.22–0.89), whereas no association was observed in postmenopausal women. Other soy foods showed no association with CVD incidence. Dietary soy isoflavones and total soy foods are associated with a decreased CVD risk in premenopausal women. Among soy foods, only tofu showed significant health benefits.

Download Full-text

Association among age, gender, menopausal status and small dense low-density lipoprotein cholesterol: a cross-sectional study

BMJ Open ◽

10.1136/bmjopen-2020-041613 ◽

2021 ◽

Vol 11 (2) ◽

pp. e041613

Author(s):

Toshihide Izumida ◽

Yosikazu Nakamura ◽

Yukihiro Sato ◽

Shizukiyo Ishikawa

Keyword(s):

Postmenopausal Women ◽

Low Density Lipoprotein ◽

Menopausal Status ◽

Density Lipoprotein ◽

Premenopausal Women ◽

Cross Sectional Study ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Cross Sectional

ObjectivesSmall dense low-density lipoprotein cholesterol (sdLDL-C) might be a better cardiovascular disease (CVD) indicator than low-density lipoprotein cholesterol (LDL-C); however, details regarding its epidemiology remain elusive. The present study aimed at evaluating the association between the demographic factors, such as age, gender and menopausal status, and sdLDL-C levels and sdLDL-C/LDL-C ratio in the Japanese population.DesignThis was a cross-sectional study.Setting13 rural districts in Japan, 2010–2017.ParticipantsThis study included 5208 participants (2397 men and 2811 women), who underwent the health mass screening that was conducted in accordance with the medical care system for the elderly and obtained informed consent for this study.ResultsIn total, 517 premenopausal women (mean age ±SD, 45.1±4.2 years), 2294 postmenopausal women (66.5±8.8 years) and 2397 men (64.1±11.2 years) were analysed. In men, the sdLDL-C levels and sdLDL-C/LDL-C ratio increased during younger adulthood, peaked (36.4 mg/dL, 0.35) at 50–54 years, and then decreased. In women, relatively regular increasing trends of sdLDL-C level and sdLDL-C/LDL-C ratio until approximately 65 years (32.7 mg/dL, 0.28), followed by a downward or pleated trend. Given the beta value of age, body mass index, fasting glucose and smoking and drinking status by multiple linear regression analysis, standardised sdLDL-C levels and sdLDL-C/LDL-C ratio in 50-year-old men, premenopausal women and postmenopausal women were 26.6, 22.7 and 27.4 mg/dL and 0.24, 0.15 and 0.23, respectively. The differences between premenopausal and postmenopausal women were significant (p<0.001).ConclusionsSdLDL-C and sdLDL-C/LDL-C ratios showed different distributions by age, gender and menopausal status. A subgroup-specific approach would be necessary to implement sdLDL-C for CVD prevention strategies, fully considering age-related trends, gender differences and menopausal status.

Download Full-text

Circulating Receptor Activator of Nuclear Factor-κB (RANK), RANK ligand (RANKL), and Mammographic Density in Premenopausal Women

Cancer Prevention Research ◽

10.1158/1940-6207.capr-18-0199 ◽

2018 ◽

Vol 11 (12) ◽

pp. 789-796 ◽

Cited By ~ 2

Author(s):

Adetunji T. Toriola ◽

Catherine M. Appleton ◽

Xiaoyu Zong ◽

Jingqin Luo ◽

Katherine Weilbaecher ◽

...

Keyword(s):

Mammographic Density ◽

Premenopausal Women ◽

Nuclear Factor Κb ◽

Nuclear Factor ◽

Rank Ligand ◽

Receptor Activator

Download Full-text

TREATMENT OF POSTMENOPAUSAL OSTEOPOROSIS WITH OESTROGENS AND ANDROGENS

Acta Endocrinologica ◽

10.1530/acta.0.xxxiv0051 ◽

1960 ◽

Vol XXXIV (I) ◽

pp. 51-59 ◽

Cited By ~ 14

Author(s):

C. A. Hernberg

Keyword(s):

Postmenopausal Women ◽

Postmenopausal Osteoporosis ◽

Age Group ◽

Intermittent Treatment ◽

Considerable Loss

ABSTRACT Fifteen patients with postmenopausal osteoporosis and 51 postmenopausal women without osteoporosis were subjected to intermittent treatment with oestrogens and androgens during 2 to 8 years. In the patients with osteoporosis there was prior to treatment a considerable loss of height which ceased more or less during therapy. In the nonosteoporotic postmenopausal women there was a negligible reduction in height during treatment in comparison to control cases of the same age group.

Download Full-text