Genetic Predictors of Intervertebral Disc Degeneration: Pilot Study

Abstract

Intervertebral disk degeneration (IVDD) is a dystrophic multifactorial, chronic, recurrent disease, its associated pain and neurological syndromes are among the most important problems in modern medicine. The etiology of IVDD includes both endogenous and exogenous risk factors. Genetic studies conducted to date have not identified a single gene responsible for the development of IVDD. A pilot study examined the allele and genotypic frequencies of single-nucleotide variants in the genome that play a role in the development of IVDD, depending on the pathophysiological mechanisms underlying its development. The study examined genes encoding fibrillar collagens, which are associated with cartilage mechanical stability, as well as genotypes of proinflammatory mediators, which influence IVD damage and increase the risk of herniation. The study involved 80 patients (40 men and 40 women) with chronic pain in the lower back and the presence of signs of degeneration of intervertebral discs at the lumbar level according to MRI aged 18 to 75 years (mean age 52.2 ± 2.3 years). Real-time polymerase chain reaction was used to detect single nucleotide variants (SNVs): rs1107946 of the COL1A1 gene, rs1799983 and rs2070744 of the NOS3 gene, rs1800795 of the IL6 gene. Genotyping of patients with a traumatic-extrusion phenotype of IVDD was performed in comparison with a degenerative-protrusive phenotype as a control. A pilot study led to the hypothesis that the studied variants of the NOS3 gene (rs1799983, rs2070744) and the IL6 gene (rs1800795), encoding inflammatory mediators, may be associated with an increased risk of traumatic-extrusion phenotype of IVDD, as well as the studied variant of the COL1A1 gene (rs1107946). Genetic testing of patients with various phenotypes of IVDD to identify the carriage of risk alleles of these genetic variants, and the study of their association with the rate of progression of IVDD is promising for the development of a personalized strategy for the diagnosis and dispensary observation of the patients.