Related Experiment Video
Updated: Dec 15, 2025
Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis
Published on: June 9, 2018
Circulating microRNAs Profile in Patients With Transthyretin Variant Amyloidosis
Gian Luca Vita1, M'Hammed Aguennouz2,3, Francesca Polito2
1Nemo Sud Clinical Centre for Neuromuscular Disorders, Messina, Italy.
Abstract:
Transthyretin variant amyloidosis (ATTRv) is a rare autosomal dominant disease characterized by the accumulation of amyloid in many organs, mostly causing a sensory-motor neuropathy, cardiomyopathy, and dysautonomia. The aim of the study was to report microRNAs (miRNAs) expression profile identified in the blood of ATTRv patients. Ten ATTRv patients, 10 asymptomatic carriers of transthyretin variant (TTRv), 10 patients with Charcot-Marie-Tooth (CMT) disease, and 10 healthy controls were studied. Human Schwann cells cultures were used to study the regulatory effects of miR-150-5p on the expression of cAMP response element-binding protein (CREB), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF). ATTRv patients had 33 miRNAs up-regulated and 48 down-regulated versus healthy controls; 9 miRNAs were up-regulated and 30 down-regulated versus CMT patients; 19 miRNAs were up-regulated and 38 down-regulated versus asymptomatic TTRv carriers. Twelve out of the 19 upregulated miRNAs had a fold increase higher than 100. The validation experiment indicated miR-150-5p as a valuable biomarker to differentiate ATTRv patients from asymptomatic TTRv carriers (AUC: 0.9728; p < 0.0001). Schwann cells culture model demonstrated that miR-150-5p is a powerful negative regulator of CREB, BDNF, and NGF genes. Identification of deregulated miRNAs can help in understanding the complex pathomechamism underlying the development of ATTRv and related multisystemic pathology. Further investigations are needed on the role of circulating miR-150-5p to predict the shift of TTRv carriers from an asymptomatic status to symptoms appearance.
Insights
MicroRNAs (miRNAs) in blood can distinguish transthyretin variant amyloidosis (ATTRv) patients from carriers. MiR-150-5p shows potential as a biomarker for ATTRv, regulating key nerve growth factors.
Area of Science:
- Genetics and Molecular Biology
- Neurology
- Biomarker Discovery
Background:
- Transthyretin variant amyloidosis (ATTRv) is a rare, autosomal dominant disease causing multisystemic pathology, primarily neuropathy, cardiomyopathy, and dysautonomia.
- Understanding the molecular mechanisms of ATTRv is crucial for early diagnosis and therapeutic development.
Purpose of the Study:
- To identify and profile microRNA (miRNA) expression in the blood of ATTRv patients.
- To investigate the potential of specific miRNAs as biomarkers for ATTRv.
- To explore the regulatory role of miR-150-5p in nerve cell function.
Main Methods:
- Comparative analysis of miRNA expression profiles in blood from ATTRv patients, asymptomatic carriers, Charcot-Marie-Tooth patients, and healthy controls.
- Validation of candidate biomarkers using receiver operating characteristic (ROC) curve analysis.
- In vitro study using human Schwann cells to assess the regulatory effects of miR-150-5p on CREB, BDNF, and NGF gene expression.
Main Results:
- ATTRv patients exhibited distinct miRNA expression profiles compared to healthy controls, CMT patients, and asymptomatic carriers.
- A significant number of miRNAs were found to be up-regulated or down-regulated in ATTRv patients.
- MiR-150-5p was identified as a potential biomarker, effectively differentiating ATTRv patients from asymptomatic carriers (AUC: 0.9728, p < 0.0001).
- MiR-150-5p demonstrated a potent negative regulatory effect on CREB, BDNF, and NGF gene expression in Schwann cells.
Conclusions:
- Circulating miRNA profiles can aid in understanding ATTRv pathogenesis.
- MiR-150-5p is a promising biomarker for distinguishing ATTRv patients from asymptomatic carriers.
- MiR-150-5p's regulatory role in nerve growth factors suggests its involvement in ATTRv-related neuropathy.
- Further research is warranted to explore miR-150-5p's predictive value for disease progression in TTRv carriers.
More Related Videos
Related Concept Videos
01:22MicroRNAs
01:22MicroRNAs