**Background**
Intervertebral disc degeneration (IVDD) is a prevalent spinal condition characterized by structural and functional deterioration of intervertebral discs, driven by aging, mechanical stress, and genetic predisposition. Collagen, the primary structural protein of the extracellular matrix (ECM) in discs, provides tensile strength and resilience. Genetic variations in collagen-encoding genes may disrupt collagen homeostasis, contributing to IVDD susceptibility and progression. This comprehensive review critically examines the literature on such genetic variations and their implications for IVDD, aiming to elucidate molecular mechanisms and explore clinical applications.
**Methods**
The review synthesizes findings from multiple studies, including genome-wide association studies (GWAS), twin studies, and candidate gene analyses. It discusses methods for studying genetic variations such as GWAS, next-generation sequencing (NGS), and bioinformatic tools (e.g., Human Splicing Finder, MaxEntScan). The review focuses on collagen-encoding genes (COL1A1, COL1A2, COL2A1, COL3A1, COL9A1, COL9A2, COL9A3, COL11A1, COL11A2) and their association with IVDD, as well as gene-environment interactions.
**Key Results**
- Genetic factors account for approximately 75% of IVDD susceptibility, as established by twin studies.
- The rs1800012 polymorphism in COL1A1 is associated with an increased risk of IVDD.
- Polymorphisms in COL1A1, COL9A1, COL9A2, COL9A3, COL11A1, and COL11A2 are identified as critical factors influencing IVDD susceptibility.
- Mutations in COL9 genes affect disc degeneration in both mice and humans.
- Variations in IL6 and other cytokine genes are also linked to IVDD with sciatica.
- Genetically predicted triglycerides mediate the association between type 2 diabetes mellitus and IVDD.
- The review notes that type II collagen constitutes 50%-70% of total disc collagen, with type I predominant in the outer annulus fibrosus.
- Collagen content shifts from type II to type I during degeneration, indicative of fibrosis.
**Clinical Implications**
The identification of specific genetic markers offers potential for personalized risk assessment and targeted interventions. Genetic testing for IVDD risk prediction is emerging, though it requires validation in large clinical cohorts. Personalized medicine approaches could tailor prevention and treatment based on individual genetic profiles. However, challenges include interpreting variants of unknown clinical significance, locus heterogeneity, ethical dilemmas (e.g., incidental findings), cost-effectiveness, and healthcare disparities. The review emphasizes the need for collaborative efforts to standardize genetic testing methodologies and translate discoveries into clinical practice.