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1.
Gynecol Endocrinol ; 40(1): 2329714, 2024 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-38499020

RESUMEN

OBJECTIVE: To explore the association between anxiety and frailty in community-dwelling postmenopausal women. METHODS: This was a cross-sectional study in which 390 postmenopausal women (aged 60-83 years) who were attending a comprehensive care program were surveyed between January 2018 and February 2020. Each participant was administered a validated Spanish version of the Hospital Anxiety and Depression Scale (HADS) to assess their anxiety status. Those scoring 8 or higher on the anxiety subscale of the HADS were indicative of anxiety. The assessment of frailty utilized the Fried's phenotype, with a diagnosis of frailty established if the participant met at least three out of the five criteria. Factors associated with frailty were analyzed using multivariate logistic regression. RESULTS: The mean age of participants was 70.08 years, with an average of 12.58 ± 3.19 years since menopause. Frailty was diagnosed in 43.85% of the total series, while anxiety was present in 41.08%, rising to 69.59% in participants with frailty. Neither body mass index, years since menopause, educational level, economic status, nor smoking habit demonstrated significant associations with frailty. Upon multivariate analysis, anxiety (OR 8.56), multimorbidity (OR 2.18), and age (OR 2.73) emerged as independently associated with frailty (p < .001, p = .005, and p < .001, respectively). CONCLUSIONS: Among postmenopausal women with frailty, anxiety was detected in over two thirds of cases and was independently associated with frailty. This underscores the relevance of implementing anxiety screening in comprehensive care programs for postmenopausal women, with the goal of improving frailty through anxiety diagnosis and treatment.


Asunto(s)
Fragilidad , Humanos , Femenino , Anciano , Fragilidad/epidemiología , Posmenopausia , Estudios Transversales , Menopausia , Ansiedad/epidemiología
2.
Gynecol Endocrinol ; 37(3): 269-272, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33480311

RESUMEN

OBJECTIVE: Endothelial dysfunction and denudation are considered a first step in atherosclerosis. Endothelial proliferation is key for cellular repair. The effect of bazedoxifene on the vascular endothelium has not been explored. We investigated the effect of bazedoxifene on endothelial cell proliferation. METHODS: Primary cultures from human umbilical artery endothelial cells were used in dose-response experiments (0.1, 1.0, and 10.0 EC50 dose) with bazedoxifene, estradiol, raloxifene and a combination of bazedoxifene and estradiol. Proliferation was assessed with the XTT colorimetric cell-proliferation assay. The possible participation of cyclins A, B, D1 and p27Kip1 was analyzed by the measurement of their expression at both the protein and the gene levels. RESULTS: A significant increase of similar size for cell proliferation was obtained with bazedoxifene, estradiol and raloxifene, but no significant change was observed for the association of bazedoxifene and estradiol. The impact was detected at the first 0.1 EC50 dose and was not dose-dependent. Estradiol achieved a significant increase in the protein expression of cyclin A and p27Kip1, but no change was detected for the other compounds at either the gene or protein level. CONCLUSION: Bazedoxifene demonstrated a proliferative effect of similar size to estradiol in cultured human umbilical artery endothelial cells. The molecular mechanisms need further investigation.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Células Endoteliales/efectos de los fármacos , Indoles/farmacología , Proliferación Celular/genética , Células Cultivadas , Ciclina A/genética , Ciclina A/metabolismo , Ciclina B/genética , Ciclina B/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Células Endoteliales/fisiología , Endotelio Vascular/citología , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Recién Nacido , Embarazo , Arterias Umbilicales/citología
3.
J Assist Reprod Genet ; 36(4): 697-708, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30656502

RESUMEN

PURPOSE: The present study aims to ascertain whether there is a causal relationship between women's disease conditions present at the starting time of the first intended oocyte retrieval cycle and IVF/ICSI outcomes, primarily odds of live birth in the first IVF/ICSI treatment. METHODS: This is a retrospective study of infertile healthy and diseased women that had a live birth and/or exhibited a complete first oocyte retrieval cycle. Generalized Estimating Equations (GEE) models were applied to adjust standard errors for the potential correlation among women exhibiting the same infertility etiology. Confounders to be controlled for in these GEE models were previously selected following a strict stepwise methodology. RESULTS: Compared to healthy women, diseased women exhibited lower odds of live birth (OR (95% CI) 0.704 (0.576-0.860)). Further screening analyses indicated that subclinical iodine-deficiency hypothyroidism together with autoimmune thyroiditis contributed significantly to decrease odds of live birth (OR (95% CI) 0.720 (0.608-0.853)). Another important contribution arose from practically all the remaining morbid conditions analyzed. These diseases were individually associated with lower odds of live birth, although differences were non-significant. Notwithstanding, differences became significant after merging these diseases in a single group (OR (95% CI) 0.605 (0.394-0.930)). CONCLUSION: There is a significant causal association between most diseases present at the starting time of the first intended oocyte retrieval cycle and lower odds of live birth in the first IVF/ICSI treatment.


Asunto(s)
Fertilización In Vitro , Infertilidad/epidemiología , Inducción de la Ovulación/métodos , Inyecciones de Esperma Intracitoplasmáticas , Adulto , Tasa de Natalidad , Transferencia de Embrión/métodos , Femenino , Humanos , Infertilidad/fisiopatología , Nacimiento Vivo , Recuperación del Oocito/métodos , Embarazo , Resultado del Embarazo , Índice de Embarazo , Técnicas Reproductivas Asistidas , Estudios Retrospectivos
4.
Calcif Tissue Int ; 97(5): 495-505, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26163235

RESUMEN

Osteoporosis is a common skeletal disorder characterized by increased risk of bone fracture (BF) due to fragility. BFs, particularly hip fracture, are a major concern in health care because of the associated morbidity and mortality, mainly in the elderly. Lately the involvement of epigenetic mechanisms in the pathophysiology of many diseases has been recognized. In this context, the identification of microRNAs (miRNAs) specific to BF should represent a substantial step forward in diagnostics and therapeutics. The present study aimed to identify specific miRNAs in osteoporotic BF patients compared to those in osteoarthritic controls. In the profiling stage, total RNA was extracted from serum, two pools were prepared, and then retro-transcribed in triplicate. Levels of 179 serum miRNAs were analyzed by real-time PCR, and 42 of them showed significance (P < 0.05), and 12 passed the false discovery rate test for multiple comparisons. Six miRNAs were selected for the replication stage and individually analyzed in sera from 15 BF patients and 12 controls. Results showed that 3 miRNAs (miR-122-5p, miR-125b-5p, and miR-21-5p) were valuable upregulated biomarkers in BF with respect to controls and, significantly, their levels were not affected by hemolysis. For miR-21-5p, the difference detected between groups was independent of age (P = 0.005) and its levels correlated to those of CTx (r = 0.76; P < 0.00001), a marker of bone resorption. In conclusion, several miRNAs may be biomarkers of BF, particularly miR-21-5p. Further studies are needed in order to better characterize the levels of these miRNAs in other bone diseases and to elucidate the mechanism involved in the association of these three miRNAs with osteoporotic BF.


Asunto(s)
MicroARNs/sangre , Fracturas Osteoporóticas/sangre , Fracturas Osteoporóticas/genética , Absorciometría de Fotón , Anciano , Biomarcadores/sangre , Densidad Ósea , Femenino , Perfilación de la Expresión Génica , Humanos , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , España , Transcriptoma
5.
J Bone Miner Metab ; 32(6): 691-8, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24337955

RESUMEN

Gene candidate and genome-wide association studies have revealed tens of loci of susceptibility for osteoporosis. Some limitations such as sample size, use of confounding variables, and control for multiple testing and for population stratification, however, represent common problems in these studies that make replication in independent cohorts desirable and even necessary. The main objective of the present study is to replicate previous data on three functional polymorphisms in a cohort of Spanish women. To that end, we performed an association study of three functional polymorphisms previously associated with bone phenotypes in the LRP5, TNFRSF11B, and FGFBP1 genes with low bone mineral density (BMD) in a cohort of 721 Spanish women, most of them postmenopausal. We detected a strong significant association, even when correcting for multiple comparisons, for polymorphism rs312009 in the LRP5 gene with low BMD at the lumbar-spine site. These were women with the CC genotype, which showed the worst bone parameters. Moreover, these women had a higher risk of osteoporosis (adjusted odds ratio 2.82, P = 0.001) than women with the TT/TC genotype. This association seems to be caused because the rs312009 single nucleotide polymorphism (SNP) is located at a binding site for the transcription factor RUNX2 at the 5' region of the LRP5 gene, and the T allele seems to be a better transcriber than the C allele. Regarding the other two SNPs, only the rs4876869 SNP in the TNFRSF11B gene showed a suggestive trend for both skeletal sites. These results underscore the significance of the LRP5 gene in bone metabolism and emphasize the significance of the replication of previous results in independent cohorts.


Asunto(s)
Densidad Ósea/genética , Proteínas Portadoras/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Proteína-5 Relacionada con Receptor de Lipoproteína de Baja Densidad/genética , Osteoporosis Posmenopáusica/genética , Osteoprotegerina/genética , Polimorfismo de Nucleótido Simple , Alelos , Femenino , Genotipo , Humanos , Persona de Mediana Edad , España
6.
Menopause ; 31(7): 634-640, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38743912

RESUMEN

OBJECTIVE: Frailty may be increased by menopause. Physical activity has been proposed to reduce frailty, but poor adherence and cost limit effectiveness. We aimed to investigate both the effectiveness against the frailty burden and the adherence rate of a multicomponent physical activity scheme partially managed by the participating women themselves. METHODS: Prospective controlled study consisting of a twice-weekly group physical activity scheme divided into two consecutive periods, one supervised by a health professional (12 wk) and the other supervised by the women themselves (36 wk). Group cohesion and mutual support during the patient-only period were aided by social networking via smartphones. Community-dwelling postmenopausal women were divided into a physical activity group (PAG = 126) and a usual activity control group (UAG = 126), both assessed at baseline and at the end of the study. Participants self-assigned to one of the two study arms. RESULTS: Overall, women in the PAG were more likely to improve their frailty status (60.2% vs 42.6%, P < 0.05). The frailty reversal rate from prefrail to robust was significantly higher in the PAG than in the UAG (34.04 vs 8.00%, P < 0.05). Logistic regression confirmed that women in the PAG were more likely to improve their frailty phenotype (odds ratio [OR], 9.12; 95% confidence interval [CI], 3.45-31.52; P < 0.001). Adherence, defined by participants attending 75% of sessions, was attained by 56.35% of women at 48 wk. CONCLUSION: A physical activity scheme implemented to improve frailty proved effective and attained acceptable adherence. Conditions in the peer-supervised 36-wk phase may increase sustainability.


Asunto(s)
Ejercicio Físico , Fragilidad , Cooperación del Paciente , Posmenopausia , Humanos , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Ejercicio Físico/fisiología , Fragilidad/prevención & control , Cooperación del Paciente/estadística & datos numéricos , Posmenopausia/fisiología , Anciano , Terapia por Ejercicio/métodos
7.
Maturitas ; 171: 40-44, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37001478

RESUMEN

BACKGROUND: Dynapenia increases with age and in the case of women is possibly influenced by menopause, yet whether vitamin D affects this increase remains controversial. The influence of genetic variants (single nucleotide polymorphisms) of the vitamin D receptor on dynapenia is an understudied area. AIM: To analyze the association between genetic variants of the vitamin D receptor gene and dynapenia in a cohort of community-dwelling postmenopausal women. METHODS: We performed a cross-sectional study of 463 women in a university hospital. Grip strength was used as an indicator of dynapenia. Differences in grip strength among single nucleotide polymorphisms rs11568820 and rs2228570 genotypes of the vitamin D receptor gene were assessed after adjusting for confounding variables, and the percentage of phenotypic variance was estimated by linear regression. RESULTS: Dynapenia (grip strength <20 kg) was diagnosed in 178 of the women (38.45 %). A difference in grip strength, corresponding to variants of the vitamin D receptor gene single nucleotide polymorphism rs11568820, was found when using an additive model of inheritance, with lower grip strength for the TT genotype (ANOVA, p = 0.030, close to the 0.025 significance level determined by Bonferroni correction). Assuming a recessive inheritance model for allele T, the between-group difference in grip strength was significant (TT = 19.79 ± 3.10 kg vs. CC/CT = 21.58 ± 3.49 kg, p = 0.008) after adjusting for age, body mass index, comorbidities, and sociodemographic variables. More women with dynapenia had the TT genotype (60.71 %) than the CC or CT genotype (37.01 %) (p = 0.012). CONCLUSION: This study demonstrates that the TT genotype of the rs11568820 SNP of the vitamin D receptor gene was associated with decreased grip strength in community-dwelling postmenopausal women.


Asunto(s)
Posmenopausia , Receptores de Calcitriol , Humanos , Femenino , Receptores de Calcitriol/genética , Posmenopausia/genética , Estudios Transversales , Vitamina D , Polimorfismo de Nucleótido Simple , Genotipo
8.
Maturitas ; 178: 107841, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37660598

RESUMEN

Cancer is one of the main noncommunicable diseases in terms of health impact. Factors such as a progressively aging population point to future increases in the incidence of cancer on a global level. The elevated number of affected individuals, together with continuous improvements in cancer prevention and therapy, is creating a growing population of cancer survivors, with often inadequately met needs. Lifestyle is a key modulator of cancer risk and of associated morbidity and mortality, and is included in all approaches to the long-term management of cancer. Diet is a principal component of lifestyle, and most of the available evidence is centered on the Mediterranean diet. Our objective was to provide a narrative review of the evidence on the effect of the Mediterranean diet on cancer risk and health threats related to cancer survivorship. For this purpose, we searched the PubMed database for articles published between January 1, 2000, and June 12, 2023. Current data show that the Mediterranean diet is inversely associated with risk, or is risk neutral, for most types of cancer. Tumors of the digestive system have received preferential interest, but studies have also been published on tumors in other organs. The evidence, however, is meager due to the observational nature of most studies, although it is reassuring that benefit is reproduced in studies performed in different populations and environments. Evidence related to cancer survivors is limited by the paucity of studies, yet several findings regarding survival, recurrence, and short- and long-term morbidity suggest a potential role for the Mediterranean diet that warrants further research.


Asunto(s)
Supervivientes de Cáncer , Dieta Mediterránea , Neoplasias , Humanos , Anciano , Supervivencia , Neoplasias/etiología , Neoplasias/prevención & control , Riesgo
9.
Children (Basel) ; 10(7)2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37508717

RESUMEN

Obesity is a multifactorial disease whose onset and development are shaped by the individual genetic background. The melanocortin 4 receptor gene (MC4R) is involved in the regulation of food intake and energy expenditure. Some of the single nucleotide polymorphisms (SNPs) of this gene are related to obesity and metabolic risk factors. The present study was undertaken to assess the relationship between three polymorphism SNPs, namely, rs17782313, rs17773430 and rs34114122, and obesity and metabolic risk factors. One hundred seventy-eight children with obesity aged between 7 and 16 years were studied to determine anthropometric variables and biochemical and inflammatory parameters. Our results highlight that metabolic risk factors, especially alterations in carbohydrate metabolism, were related to rs17782313. The presence of the minor C allele in the three variants (C-C-C) was significantly associated with anthropometric measures indicative of obesity, such as the body mass and fat mass indexes, and increased the values of insulinemia to 21.91 µIU/mL with respect to the wild type values. Our study suggests that the C-C-C haplotype of the SNPs rs17782313, rs17773430 and rs34114122 of the MC4R gene potentiates metabolic risk factors at early ages in children with obesity.

10.
Maturitas ; 168: 7-12, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36370490

RESUMEN

BACKGROUND: Telehealth has emerged as an alternative to conventional, face-to-face visits, and the COVID pandemic has hastened its introduction. Telephone appointments make use of an easy-to-use and accessible technology. AIM: To investigate the usability of telephone-based telehealth in a women's health outpatient clinic and whether this may be affected by the severity of the COVID pandemic. METHOD: A telephone survey was prepared to explore two usability domains: interaction quality (4 items) and satisfaction, preference and future use (6 items). Women were selected from two periods during the COVID pandemic when the infection rates were high and low. RESULTS: The survey was completed by 106 women (60 when the prevalence of COVID was high, mean age 53.58 years, and 46 when it was low, mean age 48.59 years) out of the 153 women who had a telephone appointment. The severity of the COVID pandemic showed an effect on responses. Women were less enthusiastic about using the telephone during the period of low COVID prevalence, as shown by lower scores on 3 of the 4 items of the first domain [I had enough time; I would have understood better in person; I would have expressed myself better in person (p < 0.001 for comparison between groups on each of the 3 items)], and on 4 of the 6 items in the second domain [satisfied with quality of care (p < 0.001), or with the information received (p = 0.018); use of telephone in future (p < 0.001); preference to try other technologies in future (p < 0.001)]. Overall, women expressed a preference for in-person visits regardless of COVID prevalence rates. CONCLUSION: Telephone calls were a feasible alternative to face-to-face visits in a women's health outpatient clinic, but the pandemic pressure modified usability parameters. Respondents preferred in-person visits at any pandemic stage.


Asunto(s)
COVID-19 , Prestación Integrada de Atención de Salud , Telemedicina , Humanos , Femenino , COVID-19/epidemiología , Pandemias , Salud de la Mujer
11.
Metabolites ; 12(8)2022 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-35893245

RESUMEN

Bone pathologies such as osteoporosis (OTP) and osteoarthritis (OA) are rising in incidence with the worldwide rise in life expectancy. The diagnosis is usually obtained using imaging techniques such as densitometry, but with both being multifactorial diseases, several molecular mechanisms remain to be understood. Metabolomics offers the potential to detect global changes which can lead to the identification of biomarkers and a better insight in the progress of the diseases. Our aim was to compare the metabolic profiles of a cohort of 100 postmenopausal women, including subcapital hip fragility fracture patients, women with severe OA of the hip that required the implantation of a hip prosthesis and controls, to find altered metabolites and networks. Nuclear magnetic resonance (NMR) spectroscopy was used to obtain the metabolomic profiles of peripheral blood derived serum, and statistical analysis was performed using MATLAB V.6.5. 30 of the 73 metabolites analysed showed statistically significant differences in a 3-way ANOVA, and 11 of them were present in the comparison between OA and controls after adjustment by covariates, including amino acids, energy metabolism metabolites and phospholipid precursors. PLS-DA analysis shows a good discrimination between controls and fracture subjects with OA patients, and ROC curve analysis demonstrates that control and fracture subjects were accurately discriminated using the metabolome, but not OA. These results point to OA as an intermediate metabolic state between controls and fracture, and suggest that some metabolic shifts that happen after a fracture are also present at weaker intensity in the OA process.

12.
Sci Rep ; 11(1): 19372, 2021 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-34588560

RESUMEN

The rising incidence of bone pathologies such as osteoporosis and osteoarthritis is negatively affecting the functional status of millions of patients worldwide. The genetic component of these multifactorial pathologies is far from being fully understood, but in recent years several epigenetic mechanisms involved in the pathophysiology of these bone diseases have been identified. The aim of the present study was to compare the serum expression of four miRNAs in women with hip fragility fracture (OF group), osteoarthritis requiring hip replacement (OA group) and control women (Ctrl group). Serum expression of miR-497-5p, miR-155-5p, miR-423-5p and miR-365-3p was determined in a sample of 23 OA women, 25 OF women and 52 Ctrl women. Data shown that women with bone pathologies have higher expression of miR-497 and miR-423 and lower expression of miR-155 and miR-365 than control subjects. Most importantly, miR-497 was identified as an excellent discriminator between OA group and control group (AUC: 0.89, p < 0.000) and acceptable in distinguishing from the OF group (AUC: 0.76, p = 0.002). Our data suggest that circulating miR-497 may represent a significant biomarker of OA, a promising finding that could contribute towards future early-stage diagnosis of this disease. Further studies are required to establish the role of miR-155, miR-423 and miR-365 in bone pathologies.


Asunto(s)
MicroARNs/sangre , Osteoartritis/sangre , Osteoporosis/sangre , Fracturas Osteoporóticas/sangre , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad
13.
Medicine (Baltimore) ; 100(23): e26216, 2021 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-34115005

RESUMEN

ABSTRACT: There is debate on the role of estrogens in modulating the risk for atherosclerosis in women. Our purpose was to investigate whether the size of the estrogenic impact was independently associated with variation of carotid intima-media thickness (IMT) in healthy late postmenopausal women. The levels of circulating estrogens have been used in previous studies but the influence of SNPs of the estrogen receptors (ER) α and ß have not been investigated.We performed a crossed-sectional study of 91 women in a university hospital. We used a double approach in which, in addition to the measurement of estradiol levels by ultrasensitive methods, genetic variants (SNPs) associated with differing expression of the ER α and ß genes were assessed. Multivariable analysis was used to examine the association of candidate factors with the value of IMT and plaque detection at both the carotid wall and the sinus.A genotype combination translating reduced gene expression of the ERß was directly associated with IMT at both the carotid wall (P = .001) and the sinus (P = .002). Other predictors of IMT were the levels of glucose, positively associated with IMT at both the carotid wall (P < .001) and the sinus (P = .001), age positively associated with IMT at the sinus (P = .003), and levels of vitamin D, positively associated with IMT at the carotid wall (P = .04).Poorer estrogenic impact, as concordant with a SNP variant imposing reduced expression of the ERß, was directly associated with IMT at both the carotid wall and the sinus. Glucose level, vitamin D only for the carotid wall, and age only for the sinus, also emerged as independent factors in the IMT variance.


Asunto(s)
Grosor Intima-Media Carotídeo/estadística & datos numéricos , Receptor beta de Estrógeno/genética , Posmenopausia , Anciano , Biomarcadores/análisis , Biomarcadores/sangre , Grosor Intima-Media Carotídeo/instrumentación , Estudios Transversales , Receptor beta de Estrógeno/sangre , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Hospitales Universitarios/organización & administración , Hospitales Universitarios/estadística & datos numéricos , Humanos , Modelos Lineales , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Factores de Riesgo , Ultrasonografía/métodos
14.
Genes (Basel) ; 12(12)2021 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-34946961

RESUMEN

Much of the genetic variance associated with osteoporosis is still unknown. Bone mineral density (BMD) is the main predictor of osteoporosis risk, although other anthropometric phenotypes have recently gained importance. The aim of this study was to analyze the association of SNPs in genes involved in osteoblast differentiation and function with BMD, body mass index (BMI), and waist (WC) and hip (HC) circumferences. Four genes that affect osteoblast differentiation and/or function were selected from among the differentially expressed genes in fragility hip fracture (FOXC1, CTNNB1, MEF2C, and EBF2), and an association study of four single-nucleotide polymorphisms (SNPs) was conducted in a cohort of 1001 women. Possible allelic imbalance was also studied for SNP rs87939 of the CTNNB1 gene. We found significant associations of SNP rs87939 of the CTNNB1 gene with LS-sBMD, and of SNP rs1366594 of the MEF2C gene with BMI, after adjustment for confounding variables. The SNP of the MEF2C gene also showed a significant trend to association with FN-sBMD (p = 0.009). A possible allelic imbalance was ruled out as no differences for each allele were detected in CTNNB1 expression in primary osteoblasts obtained from homozygous women. In conclusion, we demonstrated that two SNPs in the MEF2C and CTNNB1 genes, both implicated in osteoblast differentiation and/or function, are associated with BMI and LS-sBMD, respectively.


Asunto(s)
Osteoblastos/fisiología , Polimorfismo de Nucleótido Simple , beta Catenina/genética , Absorciometría de Fotón , Anciano , Desequilibrio Alélico , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Índice de Masa Corporal , Densidad Ósea , Diferenciación Celular , Estudios de Cohortes , Femenino , Factores de Transcripción Forkhead/genética , Estudios de Asociación Genética , Humanos , Factores de Transcripción MEF2/genética , Persona de Mediana Edad , España , Circunferencia de la Cintura
15.
Maturitas ; 147: 41-46, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33832646

RESUMEN

OBJECTIVE: Experimental studies suggest that lipids affect bone metabolism. We aimed to elucidate whether lipid levels are associated with bone mineral density (BMD) in a cohort of postmenopausal women. DESIGN: A cross-sectional study of participants in the Chronic Ailment Reduction after MENopause (CARMEN) cohort. Women underwent assessment of clinical and analytical parameters, including fasting lipid levels. BMD was assessed at both lumbar spine and hip. Homogeneity in the cohort was optimized by filtering out a series of confounding variables with a known impact on bone. MAIN OUTCOME MEASURES: Association of BMD at lumbar spine and femoral neck with lipid levels. RESULTS: A total of 667 of the 1304 screened women were analyzed. A strong correlation was revealed between total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in univariate analysis. Multivariate analysis detected a significant positive association of HDL-C with BMD at both spine (p = 0.007) and femoral neck (p = 0.013). Other independent predictors of spine BMD were years since menopause (ysm, negatively associated), and body mass index (BMI) and estradiol, both positively associated with BMD. The other independent variables in the femoral neck were ysm and glucose (negatively associated) and BMI, estradiol, and phosphate, all positively associated with BMD. CONCLUSION: Levels of HDL-C, but not TC, LDL-C or triglycerides, were positively associated with BMD at both the lumbar spine and femoral neck in a homogeneous cohort of postmenopausal women.


Asunto(s)
Densidad Ósea , HDL-Colesterol/sangre , Cuello Femoral , Vértebras Lumbares , Posmenopausia/sangre , Anciano , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad
16.
J Bone Miner Metab ; 28(6): 696-705, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20407796

RESUMEN

RUNX2 is a transcription factor essential for osteoblast differentiation and skeletal morphogenesis. Its mutation creates cleidocranial dysplasia (CCD), a disorder characterized by skeletal abnormalities and bone mineral density (BMD) alterations. The purpose of the present study has been to clarify whether polymorphisms affecting this gene could be associated with changes in BMD in women. To that end, we performed an association study of BMD values from 776 women with two single nucleotide polymorphisms (SNPs) located at P2 promoter (-1025 T>C) and at exon 2 (+198 G>A), and with a deletion polymorphism (17Ala>11Ala), also located at exon 2. We found an association of -1025 T>C SNP with femoral neck BMD (FN-BMD), being the women of TC/CC genotype who have higher BMD than women of TT genotype (P = 0.006). This association was independent of age, weight, menopausal status, or hormone replacement therapy (HRT) use as shown by regression analysis. When women of highest versus lowest quartile of BMD were compared, this association became more evident (P = 0.002), extending also to +198 G>A SNP (GA/AA women with higher FN-BMD; P < 0.05). In addition, we describe herein three novel rare variants in the polyglutamine domain of RUNX2 protein: an in-frame insertion and two deletions in exon 2, resulting in the insertions of 7 and deletions of 7 and 5 glutamines, respectively. These variants do not produce CCD, increased frequency of bone fracture, or BMD alterations. In conclusion, common polymorphisms in Runx2 are associated with FN-BMD. Nevertheless, rare variants that modify the polyglutamine domain of RUNX2 neither have any effect on BMD nor produce the CCD phenotype. These results underscore the significance of polymorphisms in the 5'-region of Runx2 in the determination of FN-BMD.


Asunto(s)
Densidad Ósea/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Cuello Femoral/química , Polimorfismo Genético , Secuencias de Aminoácidos/genética , Estudios de Cohortes , Exones , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Heterocigoto , Humanos , Menopausia , Persona de Mediana Edad , Mutación , Osteoporosis Posmenopáusica/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas , Eliminación de Secuencia , España
17.
Medicine (Baltimore) ; 99(40): e22436, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33019425

RESUMEN

In addition to governing key functions in bone metabolism and the immune system, the RANK/RANKL/OPG system plays a role in the vascular system, particularly in vascular calcification and atherosclerosis.Given that these 2 phenotypes are considered a major cause of high blood pressure (BP), in this study we analyzed the association of SNPs in RANK and OPG genes with blood pressure. An observational study was conducted of 2 SNPs in the RANK gene (rs884205 and rs78326403) and 1 in the OPG gene (rs4876869) with systolic (SBP) and diastolic blood pressure (DBP) in a cohort of 695 women.Data analysis revealed a statistically significant association between the SNP rs884205 and BP pressure (SBP and DBP). Analyzing this relationship by the dominant inheritance model for this SNP (allele risk: A), women of the AA/AC genotype showed higher BP than women of the CC genotype, both for SBP (P = .001) and for DBP (P = .003), and these associations both surpassed the Bonferroni threshold for multiple comparisons. Multivariate regression analysis including known predictors of BP as independent variables was performed to evaluate the strength of this association, which in the case of the SNP rs884205 of the RANK gene remained statistically significant after adjustment for both SBP (P = .0006) and DBP (P = .005), demonstrating the key role of this SNP in BP.We report a robust association between the SNP rs884205 in RANK gene and BP in women, and this SNP is validated as a candidate in cardiovascular risk studies.


Asunto(s)
Presión Sanguínea/genética , Receptor Activador del Factor Nuclear kappa-B/sangre , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Persona de Mediana Edad , Osteoprotegerina/sangre , Polimorfismo de Nucleótido Simple , España
18.
Sci Rep ; 10(1): 16298, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-33004909

RESUMEN

To identify new candidate genes in osteoporosis, mainly involved in epigenetic mechanisms, we compared whole gene-expression in osteoblasts (OBs) obtained from women undergoing hip replacement surgery due to fragility fracture and severe osteoarthritis. Then, we analyzed the association of several SNPs with BMD in 1028 women. Microarray analysis yielded 2542 differentially expressed transcripts belonging to 1798 annotated genes, of which 45.6% (819) were overexpressed, and 54.4% (979) underexpressed (fold-change between - 7.45 and 4.0). Among the most represented pathways indicated by transcriptome analysis were chondrocyte development, positive regulation of bone mineralization, BMP signaling pathway, skeletal system development and Wnt signaling pathway. In the translational stage we genotyped 4 SNPs in DOT1L, HEY2, CARM1 and DNMT3A genes. Raw data analyzed against inheritance patterns showed a statistically significant association between a SNP of DNMT3A and femoral neck-(FN) sBMD and primarily a SNP of CARM1 was correlated with both FN and lumbar spine-(LS) sBMD. Most of these associations remained statistically significant after adjusting for confounders. In analysis with anthropometric and clinical variables, the SNP of CARM1 unexpectedly revealed a close association with BMI (p = 0.000082), insulin (p = 0.000085), and HOMA-IR (p = 0.000078). In conclusion, SNPs of the DNMT3A and CARM1 genes are associated with BMD, in the latter case probably owing to a strong correlation with obesity and fasting insulin levels.


Asunto(s)
Proteínas Adaptadoras de Señalización CARD/genética , ADN (Citosina-5-)-Metiltransferasas/genética , Predisposición Genética a la Enfermedad/genética , Guanilato Ciclasa/genética , Osteoporosis/genética , Densidad Ósea/genética , Estudios de Casos y Controles , ADN Metiltransferasa 3A , Perfilación de la Expresión Génica/métodos , Humanos , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Fracturas Osteoporóticas/genética , Polimorfismo de Nucleótido Simple/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Transcriptoma
19.
Nutrients ; 12(10)2020 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-33081027

RESUMEN

The rates of metabolic syndrome are increasing in parallel with the increasing prevalence of obesity, primarily due to its concomitant insulin resistance. This is particularly concerning for women, as the years around menopause are accompanied by an increase in visceral obesity, a strong determinant of insulin resistance. A fall in estrogens and increase in the androgen/estrogen ratio is attributed a determining role in this process, which has been confirmed in other physiological models, such as polycystic ovary syndrome. A healthy lifestyle, with special emphasis on nutrition, has been recommended as a first-line strategy in consensuses and guidelines. A consistent body of evidence has accumulated suggesting that the Mediterranean diet, with olive oil as a vital component, has both health benefits and acceptable adherence. Herein, we provide an updated overview of current knowledge on the benefits of olive oil most relevant to menopause-associated metabolic syndrome, including an analysis of the components with the greatest health impact, their effect on basic mechanisms of disease, and the state of the art regarding their action on the main features of metabolic syndrome.


Asunto(s)
Dieta Saludable , Dieta Mediterránea , Envejecimiento Saludable , Estilo de Vida Saludable , Menopausia , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Fenómenos Fisiológicos de la Nutrición/fisiología , Aceite de Oliva , Anciano , Andrógenos/metabolismo , Estrógenos/metabolismo , Femenino , Humanos , Resistencia a la Insulina , Síndrome Metabólico/terapia , Persona de Mediana Edad , Obesidad Abdominal/etiología , Obesidad Abdominal/metabolismo , Obesidad Abdominal/terapia
20.
Maturitas ; 136: 25-37, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32386663

RESUMEN

Diet is a crucial variable for a healthy life. A rapidly growing number of studies in recent years support the hypothesis that the Mediterranean diet (MedDiet) has a beneficial effect on certain body systems, but the highly varied objectives and quality of these publications warrants an updated assessment. In the present review we performed a comprehensive evaluation of current evidence on the impact of the MedDiet on human health, assessing its effect on the incidence or progression of the main non-communicable diseases and their intermediate outcomes and risk factors. We scrutinised the clinical evidence from observational studies and randomised controlled trials. Cardiovascular disease was the condition with most information. The MedDiet showed a general preventive effect, which was reproduced to varying degrees for certain intermediate cardiovascular outcomes such as blood pressure, lipids, obesity, metabolic syndrome and diabetes. Benefits were also found for several types of cancer, brain function (including cognition, mood and to a lesser extent Parkinson's disease) and mortality. The quality of the published evidence was, however, generally moderate or low. In conclusion, the MedDiet shows a favourable impact on health. General adoption of a MedDiet is concordant with current policies promoting healthy and sustainable nutrition worldwide. Nonetheless, more high-quality research is needed to improve the consistency of the findings.


Asunto(s)
Dieta Mediterránea , Enfermedades Cardiovasculares/epidemiología , Cognición , Diabetes Mellitus/epidemiología , Estudios Epidemiológicos , Humanos , Menopausia , Neoplasias/epidemiología , Estudios Observacionales como Asunto , Osteoporosis/epidemiología , Ensayos Clínicos Controlados Aleatorios como Asunto
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