Intervertebral disc degeneration in relation to the COL9A3 and the IL-1ß gene polymorphisms

Abstract

IntroductionDegeneration of the intervertebral disc is a process that begins early in life and is a consequence of a various intrinsic and extrinsic factors as well as of normal ageing. Environmental factors appear to explain only a minor part of individual variation in pathologic changes in the disc, while the major part remains unexplained [4,5,34]. Epidemiological studies of twins suggest that inheritance is the largest single determinant of disc degeneration (DD) [5,27].Recently, an association between DD and polymorphisms in the vitamin-D receptor [37,38] Abstract Disc degeneration is a complex condition in which environmental factors and multiple genes are expected to act together to determine the degenerative phenotype. Recently associations of COL9A2 (Trp2 allele) and COL9A3 (Trp3 allele) polymorphisms with lumbar disc disease characterized by sciatica have been reported. However, it is not known whether the Trp2 or Trp3 alleles contribute to disc degeneration (DD). In this study, the association between the collagen genes polymorphisms and lumbar DD was investigated. Furthermore, the influence of the IL1b(C 3954 -T) polymorphism on the association of collagen genes polymorphisms with DD was examined. Lumbar intervertebral discs of 135 middle-aged occupationally active men were evaluated with magnetic resonance imaging, using decreased signal intensity of the nucleus pulposus, disc bulges, and decreased disc height as signs of degeneration. Blood samples were analysed for the presence of COL9A3 and COL9A2 tryptophan alleles (Trp3 and Trp2 alleles). The COL11A2, COL2A1 and IL-1b(C 3954 -T) polymorphisms were also analysed. Multivariate logistic regression analysis allowing for occupation and body mass index showed that the carriage of the Trp3 allele in the absence of the IL1bT 3954 allele increased the risk of dark nucleus pulposus (OR 7.0, 95% CI 1.3-38.8) and joint occurrence of degenerative changes (OR 8.0, 95% CI 1.4-44.7). There was no effect of the Trp3 allele on DD in the presence of the IL-1bT 3954 allele. The carriers of the COL11A2 minor allele had an increased risk of disc bulges (OR 2.1, 95% CI 1.0-4.2) as compared with non-carriers. The results suggest that the effect of the COL9A3 gene polymorphism on DD might be modified by the IL-1b gene polymorphism.

Segment-by-segment stabilization for degenerative disc disease: a hybrid technique

“…This has culminated in recent work that addresses the aging spine (e.g. natural history [2], inflammatory mediators [39], radiological changes [48], genomic factors [45], hereditary effects [49], and osteoporotic fracture modeling [27]) and specific aspects of the degenerative cascade (e.g. paraspinal muscles in lumbar degenerative kyphosis [26], paraspinal denervation [21]).…”

Lumbar disc degeneration below a long arthrodesis (performed for scoliosis in adults) to L4 or L5

“…However, the mechanisms for this at a cellular level are poorly understood and it may be that other factors such as genotype [23] will prove to be the most important single factor in disc degeneration and ASD. However, this should not discourage the surgeon from obtaining the ideal mechanical environment to minimize the stresses placed upon an unfused adjacent segment when fusing the spine, i.e.…”

Associations of 25 structural, degradative, and inflammatory candidate genes with lumbar disc desiccation, bulging, and height narrowing

“…Among the 11 genes that have been investigated in 21 studies previously performed, 9 (AGC1, COL1A1, COL9A2, COL5A1, COL9A3, COL11A2, IL1, IL2, and MMP3) were associated with disc degeneration, pathologic changes, or associated symptoms in at least 1 study (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). However, phenotypes vary widely, and the studies included both symptoms assumed to be associated with disc pathology and qualitative assessments of disc degeneration.…”