Intervertebral disc degeneration in relation to the COL9A3 and the IL-1ß gene polymorphisms
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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 IL-1β(C3954-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-1β(C3954-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 IL-1βT3954 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-1βT3954 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-1β gene polymorphism.
KeywordsLumbar disc degeneration Magnetic resonance imaging COL9A3 IL-1β
This project was financially supported by the Finnish Work Environment Fund and partly by the Academy of Finland, Lousiana Gene Therapy Research Consortium (New Orleans, LA) and HCA—The Health Care Company (Memphis, TN) and by grant AR45982 from the National Institute of Health. The authors thank Sanna Kouhia for genetic analysis and Antti Lamminen, DMedSc and Markku Liuke, MD for help with visual assessment of magnetic resonance images.
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