To demonstrate the role of CILP in LDD in vivo, we generated transgenic mice that express CILP specifically in the intervertebral disc tissues and assessed whether CILP exacerbates disc degeneration.
We conclude that the CILP gene polymorphism (rs2073711) is associated with a lower risk of LDD, the MMP3 (rs591058) gene polymorphism is associated with LDD among women, and the TT genotype confers a lower risk of LDD.
Therefore, we conclude that the extracellular matrix protein CILP regulates TGF-beta signaling and that this regulation has a crucial role in the etiology and pathogenesis of LDD.
The results showed no evidence of association in the Finnish (OR = 1.35, 95% CI 0.97 to 1.87; p = 0.14) or the Chinese (OR = 1.05, 95% CI 0.77 to 1.43; p = 0.71) samples, suggesting that cartilage intermediate layer protein gene is not a major risk factor for symptoms of LDD in Caucasians or in the general population that included individuals with or without symptoms.
Recently associations of COL9A2 (Trp2 allele) and COL9A3 (Trp3 allele) polymorphisms with lumbar disc disease characterized by sciatica have been reported.
The meta-analysis of 10 case-control studies, including 2102 LDD cases and 2507 controls, indicated that COL9A2 gene (rs12077871, rs12722877, rs7533552) and COL9A3 gene (rs61734651) polymorphisms were not associated with LDD (rs12077871: T vs. C, OR = 1.85, 95% CI = 0.87-3.91, P = 0.11; rs12722877: G vs. C, OR = 0.83, 95% CI = 0.69-1.01, P = 0.06; rs7533552: G vs. A, OR = 1.11, 95% CI = 0.98-1.25, P = 0.09; rs61734651: T vs. C, OR = 1.57, 95% CI = 0.51-4.84, P = 0.43).
Its biological role has been unclear, but recent genetic studies have demonstrated association between asporin and various bone and joint diseases, including osteoarthritis, rheumatoid arthritis and lumbar disc disease.
The associating G allele in COL9A2 changes a glutamine to arginine or to tryptophan and may predispose to both hip OA and LDD, making it a candidate for degenerative connective tissue diseases.
Recently associations of COL9A2 (Trp2 allele) and COL9A3 (Trp3 allele) polymorphisms with lumbar disc disease characterized by sciatica have been reported.
However, we did see association of a COL9A2 specific haplotype with LDD (P=0.025; permutation test); this association is more significant in patients with severe lumbar disc degeneration (P=0.011).
A case-control study of the Trp2/3 alleles of COL9A2/3 genes and their correlation with occurrence of Lumbar disc disease (DDD) as phenotyped by magnetic resonance imaging.
The meta-analysis of 10 case-control studies, including 2102 LDD cases and 2507 controls, indicated that COL9A2 gene (rs12077871, rs12722877, rs7533552) and COL9A3 gene (rs61734651) polymorphisms were not associated with LDD (rs12077871: T vs. C, OR = 1.85, 95% CI = 0.87-3.91, P = 0.11; rs12722877: G vs. C, OR = 0.83, 95% CI = 0.69-1.01, P = 0.06; rs7533552: G vs. A, OR = 1.11, 95% CI = 0.98-1.25, P = 0.09; rs61734651: T vs. C, OR = 1.57, 95% CI = 0.51-4.84, P = 0.43).
The VDR AA homozygous genotype was seen in 30(16.7%) patients with LDD and 20(8.7%) controls (codominant model: OR = 2.48; 95% CI 1.30-4.73, P = .005) with an estimated approximately 2.5-fold risk of developing LDD in individuals with this genotype.