RESUMEN

The nuclear receptor coactivator 5 (NCOA5) has been linked to several inflammatory disorders, including Behçet's disease (BD). We evaluated the expression of NCOA5 messenger RNA (mRNA) using real-time reverse transcription-polymerase chain reaction, and analyzed the rs2903908 T > C of NCOA5 using TaqMan allelic discrimination assay in 49 Egyptian BD patients and 50 controls. The NCOA5 mRNA levels were higher in patients compared to controls (p = .02), female patients compared to males (p = .037), and in patients with ocular involvement (p = .049). Non-CC genotype carriers had a higher frequency of articular manifestations compared with CC carriers (p = .047). Genotypes CC + CT were associated with reduced risk of cutaneous involvement (OR = 0.27, p = .04). CC carriers with active BD or cutaneous manifestations displayed significantly lower NCOA5 mRNA expression than TT carriers. Our results demonstrate that NCOA5 is linked to BD clinical findings and activity.

Asunto(s)

Síndrome de Behçet , Coactivadores de Receptor Nuclear , Polimorfismo de Nucleótido Simple , Femenino , Humanos , Masculino , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/genética , Estudios de Casos y Controles , Egipto/epidemiología , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Coactivadores de Receptor Nuclear/genética , Coactivadores de Receptor Nuclear/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo

RESUMEN

ABSTRACT Background: MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression post-transcriptionally. Accumulating evidence indicates that the miR-30 family takes part in the development of multiple tissues and organs, and is a potential contributor to various dis eases, including autoimmune disorders such as systemic lupus erythematosus (SLE). The aim of this study was to evaluate the expression of miR-30e-5p, a member of the miR-30 fam ily, and investigate its potential relationship to clinical characteristics and possible disease activity in an Egyptian SLE cohort. Methods: Serum samples from 40 SLE patients and 37 age and gender matched healthy sub jects were tested for miR-30e-5p expression level using the Taqman quantitative reverse transcription-polymerase chain reaction. Analysis was performed using the 2 - AACT method. Results: The mean age of the patients was 28.7 ± 7.9 years, with a mean disease duration of 6.4 ±5.3 years. The median fold change in serum miR-30e-5p among our SLE cohort was significantly higher 1.748 (0.223-20.485) compared to the control group 0.877 (0.058-3.522) (P = 0.02). Receiver operating characteristic curve analysis revealed that miR-30e-5p expres sion level can discriminate SLE patients from controls at a cut-off value >1.06 with the area under the curve (AUC) = 0.676 (95% CI: 0.559-0.794, P = 0.02), with 64.3% sensitivity and 61.5% specificity. There was no correlation between any of the demographic features, clinical manifestations (apart from serositis, P = 0.013) or disease activity and miR-30e-5p levels. Conclusion: Our study demonstrated elevated miR-30e-5p expression levels in serum sam ples of SLE patients. Apart from serositis, it was not associated with any other disease characteristics.

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RESUMEN Antecedentes: Los microARN (miRNA) son ARN no codificantes que regulan la expresión de los genes después de la transcripción. Las pruebas acumuladas indican que la familia de miR-30 participa en el desarrollo de múltiples tejidos y órganos, y es un posible contribuyente a diversas enfermedades, incluidos los trastornos autoinmunes como el lupus eritematoso sistémico (LES). El objetivo de este estudio fue evaluar la expresión del miR-30e-5p, un miembro de la familia miR-30, e investigar su posible relación con las características clínicas y la posible actividad de la enfermedad en una cohorte egipcia de LES. Métodos: Se analizaron muestras de suero de 40 pacientes con LES y 37 sujetos sanos de edad y sexo similares para determinar el nivel de expresión de miR-30e-5p, utilizando la reacción en cadena de la polimerasa de transcripción inversa cuantitativa Taqman. El análisis se llevó a cabo empleando el método 2-AACT. Los resultados: La edad media de los pacientes fue de 28,7 ± 7,9 años, mientras que la duración media de la enfermedad fue de 6,4 ± 5,3 años. La mediana del cambio de pliegue del suero miR-30e-5p entre nuestra cohorte de LES fue significativamente mayor, 1,748 (0,223-20,485), en comparación con el grupo de control, 0,877 (0,058-3,522) (p = 0,02). El análisis de la curva característica de funcionamiento del receptor reveló que el nivel de expresión del miR-30e-5p puede discriminar a los pacientes con LES de los controles en un valor de corte > 1,06, con el área bajo la curva (AUC) = 0,676 (IC del 95%: 0,559-0,794; p = 0,02), una sensibilidad del 64,3% y una especificidad del 61,5%. No hubo asociación entre ninguna de las características demográficas, manifestaciones clínicas (aparte de la serositis, p = 0,013) o actividad de la enfermedad y los niveles de miR-30e-5p. Conclusión: Nuestro estudio demostró niveles elevados de expresión de miR-30e-5p en mues tras de suero de pacientes con LES. Aparte de la serositis, no se asoció con ninguna otra característica de la enfermedad.

Asunto(s)

Humanos , Femenino , Adulto , Reacción en Cadena de la Polimerasa , Enfermedades de la Piel y Tejido Conjuntivo , Ácidos Nucleicos, Nucleótidos y Nucleósidos , Procesos Patológicos , Serositis , Condiciones Patológicas, Signos y Síntomas , Elementos sin Sentido (Genética) , ARN sin Sentido , Enfermedades del Tejido Conjuntivo , MicroARNs , Lupus Eritematoso Sistémico

RESUMEN

PURPOSE: To evaluate the choroidal thickness (CT) in the macular area in patients with lupus nephritis and to compare the results with both non-nephritic patients and normal control. To assess the relation of CT to serum microRNA146, disease duration, activity index, and medications. PATIENTS AND METHODS: Thirty-five SLE patients and thirty normal healthy controls were enrolled for this cross-sectional prospective study. All participants have undergone optical coherence tomography using RTVue OCT (Optovue Inc., Fremont, CA, USA). The scan used was the macular cross 6-mm line. We measured CT from the posterior edge of the retinal pigment epithelium (RPE) to the choroid-sclera junction at subfovea, and 750 µm both temporal and nasal to the fovea. RESULTS: The mean central subfoveal CT in patients was 275.7 ± 41.0 µm (214-374 µm), and the mean central subfoveal CT in the control group was 364.5± 23.0 µm (323-411µm). There was a significant thinning at all three points in patients compared to the control group (p<0.001, Mann-Whitney U-test). In the patients group, subfoveal choroid in non-nephritic subgroup showed significant thinning compared to nephritic subgroup (p=0.032, Mann-Whitney U-test). Drusen-like deposits (DLDs) were detected in 22.9% (8/35) of patients and none in control (p=.023). MiRNA146 showed a significant positive correlation with nephritic lupus patients (r=0.036, P=0.04). CONCLUSION: The choroidal thickness was significantly thicker among the nephritic lupus patients as compared to the non-nephritic subgroup. Both SLE patients' subgroups are thinner than normal control. Subfoveal choroidal thickening can be considered a biomarker in nephritic lupus especially in conjunction with an increase in miRNA146a. All SLE patients are at risk of small Drusen-like deposits.