ABSTRACT
BACKGROUND: Marfan's syndrome (MFS) is an autosomal dominant inheritance disorder with a 1/5,000 live-birth prevalence. It is characterized by a wide range of clinical manifestations with more than 3,000 mutations identified in the FBN1 gene. In this study, we aimed to determine if specific patterns of circulating micro-RNAs (miRNAs) are associated with MFS-associated with cardiovascular diseases. METHODS: Microarray-based miRNA profiling was performed on blood samples of 12 MFS patients, and 12 healthy volunteers (HVs) controls and the differences in miRNA abundance between the two groups were validated using independent cohorts of 22 MFS and of 22 HV controls by real-time quantitative polymerase chain reaction (RT-qPCR). Enrichment analyses of altered miRNA abundance were predicted using bioinformatics tools. RESULTS: Altered miRNA abundance levels were determined between MFS (n = 34) and HVs (n = 34). In a screening phase, we analyzed 12 patients with MFS and 12 HVs by miRNA microarray. We found 198 miRNAs that were significantly altered in MFS patients as compared with HVs, including 16 miRNAs with a more than 1.5-fold change. Out of these 16 miRNAs, 10 showed a decreased abundance and 6 showed an increased abundance. In the validation phase, we analyzed independent cohorts of 22 MFS and of 22 HV controls by RT-qPCR. We confirmed the direction of abundance changes and the significance of different abundances between MFS patients and HVs for four miRNAs, namely, miR-362-5p, miR-339-3p, miR-340-5p, and miR-210-3p. Only the miR-150-5p showed a significant correlation with mitral valve prolapse (p = 0.010). The predicted targets for the validated miRNAs were associated with signal transduction, tissue remodeling, and cellular interaction pathways. CONCLUSION: The altered abundance level of different miRNAs in whole blood of MFS patients lays the ground to the development of novel diagnostic approaches with altered miRNAs levels associated with MFS with manifestations associated with cardiovascular diseases.
Subject(s)
Circulating MicroRNA/genetics , Marfan Syndrome/genetics , Transcriptome , Adolescent , Adult , Case-Control Studies , Child , Circulating MicroRNA/blood , Computational Biology , Female , Gene Expression Profiling/methods , Genetic Markers , Genetic Predisposition to Disease , Humans , Male , Marfan Syndrome/blood , Marfan Syndrome/diagnosis , Middle Aged , Oligonucleotide Array Sequence Analysis , Real-Time Polymerase Chain Reaction , Reproducibility of Results , Young AdultABSTRACT
BACKGROUND: Turner syndrome (TS) is a chromosomal disorder, in which a female is partially or entirely missing one of the two X chromosomes, with a prevalence of 1:2500 live female births. The present study aims to identify a circulating microRNA (miRNA) signature for TS patients with and without congenital heart disease (CHD). METHODS: Microarray platform interrogating 2549 miRNAs were used to detect the miRNA abundance levels in the blood of 33 TS patients and 14 age-matched healthy volunteer controls (HVs). The differentially abundant miRNAs between the two groups were further validated by RT-qPCR. RESULTS: We identified 60 differentially abundant miRNA in the blood of TS patients compared to HVs, from which, 41 and 19 miRNAs showed a higher and a lower abundance levels in TS patients compared to HVs, respectively. RT-qPCR confirmed the significantly higher abundance levels of eight miRNAs namely miR-374b-5p, miR-199a-5p, miR-340-3p, miR-125b-5p, miR-30e-3p, miR-126-3p, miR-5695, and miR-26b-5p in TS patients as compared with the HVs. The abundance level of miR-5695 was higher in TS patients displaying CHD as compared to TS patients without CHD (p = 0.0265; log2-fold change 1.99); whereas, the abundance level of miR-126-3p was lower in TS patients with congenital aortic valve disease (AVD) compared to TS patients without BAV (p = 0.0139, log2-fold change 1.52). The clinical feature statistics revealed that miR-126-3p had a significant correlation with sinotubular junction Z-score (r = 0.42; p = 0.0154). CONCLUSION: The identified circulating miRNAs signature for TS patients with manifestations associated with cardiovascular diseases provide new insights into the molecular mechanism of TS that may guide the development of novel diagnostic approaches.
Subject(s)
Circulating MicroRNA/blood , Turner Syndrome/pathology , Adolescent , Adult , Case-Control Studies , Child , Female , Heart Diseases/complications , Heart Diseases/congenital , Heart Diseases/pathology , Heart Ventricles/physiopathology , Humans , Karyotype , Turner Syndrome/complications , Turner Syndrome/genetics , Young AdultABSTRACT
We aimed in this study to investigate a possible involvement of Th17/Treg cells imbalance in autism spectrum disorders (ASD). Using flowcytometry to determine circulating Th17 and Treg cells percentages, RT- PCR and ELISA for cytokine expression, we demonstrated that Th17/Treg balance in ASD children was significantly skewed toward a Th17 response compared to their control. Th17 cells and the ratio of Th17/Treg cells had a significantly positive correlation with disease severity whereas Treg cells had a negative correlation. The imbalance of Th17, Treg cells and their related cytokines may play a vital role in the progression of the disease.