Assessment of a Single Nucleotide Variant in MIR3142HG and Its Association with the Risk of Intervertebral Disc Degeneration or Herniated Disc in Patients with Diverse Clinical Conditions

• Grant number: 25/13589-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: August 01, 2025
• End date: July 31, 2026
• Field of knowledge: Health Sciences - Collective Health - Public Health
• Principal Investigator: Manoela Marques Ortega
• Grantee: Francisca Rangelma Vieira de Meneses
• Host Institution: Universidade São Francisco (USF). Campus Bragança Paulista. Bragança Paulista , SP, Brazil

Abstract

Introduction: Intervertebral disc degeneration (IDD) and disc herniation are pathological conditions that affect the spinal column, with significant clinical and social repercussions. Studies suggest that genetic factors-particularly the expression of microRNAs (miRs) and the analysis of single nucleotide variants (SNVs)-play a critical role in the development and progression of these disorders. MiRs such as miR-27a, miR-155, miR-146a, and miR-93 are involved in regulating key cellular processes including apoptosis, inflammation, and extracellular matrix (ECM) remodeling, directly influencing disc integrity and the formation of herniated discs. Objectives: This study aims to investigate the frequency of the SNV rs17057846, located in the MIR3142HG gene, which encodes miR-3142, in a sample of Brazilian patients diagnosed with IDD or disc herniation. Additionally, the study will analyze associations between this polymorphism and clinical markers of disc degeneration, including disease severity, level of disc herniation, and intensity of inflammatory symptoms. The impact of this SNV on MIR3142 expression will also be evaluated, as well as its role in modulating the inflammatory response, with a particular focus on the ADAMTS-5 gene, which is involved in ECM degradation and disease progression. Methods: The study will include approximately 150 DNA samples extracted from herniated disc tissue of patients undergoing surgical treatment for IDD. Genotyping of the SNV rs17057846 will be performed using real-time polymerase chain reaction (RT-PCR). The expression levels of MIR3142 and its target gene ADAMTS-5 will also be quantified and correlated with different genotypes (wild-type, heterozygous, and variant) of the selected SNV, enabling a more detailed analysis of genotype-dependent modulation of the inflammatory response. Furthermore, the prevalence of each genotype will be compared across clinical variables to assess their influence on the risk and prognosis of IDD and disc herniation. Expected Results: The findings of this study may contribute to a better understanding of the molecular mechanisms underlying the progression of these spinal pathologies and support the development of more effective and personalized therapeutic strategies.