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1.
Int J Mol Sci ; 24(19)2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37834042

RESUMEN

Multiple sclerosis (MS) is a chronic and demyelinating disease with an autoimmune origin, which leads to neurodegeneration and progressive disability. Approximately 30 to 50% of patients do not respond optimally to disease-modifying therapies (DMTs), and therapeutic response may be influenced by genetic factors such as genetic variants. Therefore, our study aimed to investigate the association of the HLA-DRB1*0403 genetic variant and therapeutic response to DMTs in MS. We included 105 patients with MS diagnosis. No evidence of disease activity based on the absence of clinical relapse, disability progression or radiological activity (NEDA-3) was used to classify the therapeutic response. Patients were classified as follows: (a) controls: patients who achieved NEDA-3; (b) cases: patients who did not achieve NEDA-3. DNA was extracted from peripheral blood leukocytes. HLA-DRB1*0403 genetic variant was analyzed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. NEDA-3 was achieved in 86.7% of MS patients treated with DMTs. Genotype frequencies were GG 50.5%, GA 34.3%, and AA 15.2%. No differences were observed in the genetic variant AA between patients who achieved NEDA-3 versus patients who did not achieve NEDA-3 (48.7% vs. 43.1%, p = 0.6). We concluded that in Mexican patients with MS, HLA-DRB1*0403 was not associated with the therapeutic response to DMTs.


Asunto(s)
Esclerosis Múltiple , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/genética , Cadenas HLA-DRB1/genética , Predisposición Genética a la Enfermedad , Estudios de Casos y Controles , Genotipo
2.
Genes (Basel) ; 14(3)2023 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-36980810

RESUMEN

STAT4 plays an important role in disease activity in SLE patients. STAT4 particles have the capacity to activate the transcription of genes associated with the production of TH1 and Th17 lymphocytes, with a greater predominance on the production of IFN-γ and IL-17A. The presence of variants in STAT4 genes has a major impact on the generation of autoimmunity. However, there are few studies evaluating the impact of these variants on the production of proinflammatory cytokines such as IFN-γ and IL-17A. Methods-A case-control study was carried out with 206 Mexican mestizo patients residing in Western Mexico with a diagnosis of SLE and a group of 80 patients without autoimmune diseases was captured to determine the cut-off point for high IFN-γ levels. In this study, SLE patients with high IFN-γ levels were considered as cases (cut-off > 15.6 pg/mL), and SLE patients with normal IFN-γ levels were considered as controls (cut-off ≤ 15.6 pg/mL). Disease activity was identified from the systemic lupus erythematosus disease activity index (SLEDAI). For the determination of levels of cytokines IFN-γ, IL-12, and IL17A, commercial ELISA kits were used. Genotyping of STAT4 rs7574865 (G > T) was performed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. Results-The patients with SLE had a median age of 45 years with a range of disease duration from 4 years to 18 years; 45.6% were identified as having disease activity. In this sample, we identified a high IFN-γ prevalence of 35.4%. The levels of IFN-γ were higher in the patients with genotype TT than GG. We found that TT genotype conferred a higher risk of high IFN-γ when compared to the GG and GT genotypes. Conclusions-In this study, we identified that the polymorphic genotype TT of the STAT4 gene rs7574865 polymorphism is associated with increased levels of IFN-γ. However, its strength of association was weak, so complementary studies are needed to evaluate its impact on SLE patients.


Asunto(s)
Enfermedades Autoinmunes , Interferón gamma , Lupus Eritematoso Sistémico , Factor de Transcripción STAT4 , Preescolar , Humanos , Alelos , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/metabolismo , Estudios de Casos y Controles , Citocinas/genética , Predisposición Genética a la Enfermedad , Interferón gamma/genética , Interleucina-17/genética , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/metabolismo , Polimorfismo de Nucleótido Simple , Factor de Transcripción STAT4/genética
3.
Psychol Health Med ; 28(4): 995-1003, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-34579608

RESUMEN

The objective of the study is to determine the personal, behavioral and psychological variables associated with somatization and the number of diseases in each gender from a sample of Mexican general population. They answered a questionnaire of behavioral and psychological variables including somatization and the sum of 16 different diseases and any additional one, finally the body mass index (BMI) was measured. A total of 164 participants (women = 90, men = 74) were included. We observed that women had more somatization and number of diseases than men and that more variables (mainly psychological) were associated with somatization and with the number of diseases in women than in men. Among the variables most negatively correlated in women with both variables were sleep quality (r = -0.525 and r = -0.536, p < 0.001), self-acceptance (r = -0.460 and r = -0.501, p < 0.001), positive relations with others (r = -0.447 and r = -0.441 p < 0.001), environmental mastery (r = -0.414, p < 0.001, for both variables), purpose in life and optimism; while men only showed a low negative correlation between emotion regulation and the number of diseases (r = -0.289, p < 0.05). The positive associated variables in women were anxiety, negative emotions and depression; while men showed a lower correlation between these three variables only with somatization. The somatization and age were positively related to the number of diseases in both genders and the BMI was significantly associated with the number of diseases only in men. In conclusion, women had more somatization and number of diseases than men and also had more relation between psychological variables and the two dependent variables than men, which could in part explains the higher values of somatization and the number of diseases in women, considering that they usually present higher values of psychopathological variables.


Asunto(s)
Ansiedad , Depresión , Humanos , Masculino , Femenino , Ansiedad/epidemiología , Depresión/epidemiología , Depresión/psicología , Trastornos de Ansiedad , Encuestas y Cuestionarios
4.
J Immunol Res ; 2022: 7258152, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35592686

RESUMEN

Background: Myostatin is a regulator of muscle size. To date, there have been no published studies focusing on the relation between myostin levels and myopenia in rheumatoid arthritis (RA). Objective: Evaluate the value of serum myostatin as a biomarker of cachexia and low skeletal muscle mass (LSMM) in RA patients, along with whether high serum myostatin is associated to these conditions after adjusting for potential confounders. Methods: This cross-sectional study included 161 female RA patients and 72 female controls. In the RA group, we assessed several potential risk factors for LSMM and rheumatoid cachexia. Dual-energy X-ray absorptiometry was used to quantify the skeletal muscle mass index (SMMI) (considering LSMM ≤ 5.5 kg/m2) and the presence of rheumatoid cachexia (a fat-free mass index ≤ 10 percentile and fat mass index ≥ 25 percentile of the reference population). Serum myostatin concentrations were determined by ELISA. To identify a cut-off for high serum myostatin levels, we performed ROC curve analysis. Multivariable logistic regression analysis was used to identify the risk factors for LSMM and rheumatoid cachexia. The risk was expressed as odds ratios (ORs) and their 95% confidence intervals (95% CIs). Results: Compared to the controls, the RA group had a higher proportion of LSMM and exhibited high serum myostatin levels (p < 0.001). ROC curve analysis showed that a myostatin level ≥ 17 ng/mL was the most efficient cut-off for identifying rheumatoid cachexia (sensitivity: 53%, specificity: 71%) and LSMM (sensitivity: 43%, specificity: 77%). In the multivariable logistic regression, RA with high myostatin levels (≥17 ng/mL) was found to increase the risk of cachexia (OR = 2.79, 95% CI: 1.24-6.29; p = 0.01) and LSMM (OR = 3.04, 95% CI: 1.17-7.89; p = 0.02). Conclusions: High serum myostatin levels increase the risk of LSMM and rheumatoid cachexia. We propose that high myostatin levels are useful biomarkers for the identification of patients in risk of rheumatoid cachexia and myopenia.


Asunto(s)
Artritis Reumatoide , Caquexia , Biomarcadores , Caquexia/etiología , Estudios Transversales , Femenino , Humanos , Músculo Esquelético , Miostatina
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