Sequence variations in the collagen IX and XI genes are associated with degenerative lumbar spinal stenosis

Abstract

Background: Degenerative lumbar spinal stenosis (LSS) is usually caused by disc herniation or degeneration. Several genetic factors have been implicated in disc disease. Tryptophan alleles in COL9A2 and COL9A3 have been shown to be associated with lumbar disc disease in the Finnish population, and polymorphisms in the vitamin D receptor gene (VDR) (FokI and TaqI), the matrix metalloproteinase-3 gene (MMP-3) and an aggrecan gene (AGC1) VNTR have been reported to be associated with disc degeneration. In addition, an IVS6-4 a.t polymorphism in COL11A2 has been found in connection with stenosis caused by ossification of the posterior longitudinal ligament in the Japanese population. Objective: To study the role of genetic factors in LSS. Methods: 29 Finnish probands were analysed for mutations in the genes coding for intervertebral disc matrix proteins, COL1A1, COL1A2, COL2A1, COL9A1, COL9A2, COL9A3, COL11A1, COL11A2, and AGC1. VDR and MMP-3 polymorphisms were also analysed. Sequence variations were tested in 56 Finnish controls. Results: Several disease associated alleles were identified. A splice site mutation in COL9A2 leading to a premature translation termination codon and the generation of a truncated protein was identified in one proband, another had the Trp2 allele, and four others the Trp3 allele. The frequency of the COL11A2 IVS6 -4 t allele was 93.1% in the probands and 72.3% in controls (p = 0.0016). The differences in genotype frequencies for this site were less significant (p = 0.0043). Conclusions: Genetic factors have an important role in the pathogenesis of LSS.

Collagen 11a1 is indirectly activated by lymphocyte enhancer-binding factor 1 (Lef1) and negatively regulates osteoblast maturation

“…Further evidence for this conclusion is apparent in the Cho mice, which exhibit excess mineralization in the long bones (Seegmiller et al, 1971;Li et al, 1995). Sequence variations in the Col11a1 gene are also associated with osteoarthritis, early-onset osteoarthritis, degenerative lumbar spinal stenosis and cleft palate (Melkoniemi et al, 2003;Noponen-Hietala et al, 2003;Rodriguez et al, 2004;Jakkula et al, 2005). Its association with a variety of common diseases makes Col11a1 an important target for musculoskeletal disease research.…”

Association between the -1306C/T polymorphism of matrix metalloproteinase-2 gene and lumbar disc disease in Chinese young adults

“…Several studies have found familial predisposition to LDD, including early onset sciatica and lumbar disc herniation. In addition, mutations or polymorphisms in several genes have been reported to be associated with either the presence or severity of disc degeneration, including gene coding for collagen IX and XI [2,12,13], aggrecan [9], cartilage intermediate layer protein [18], vitamin D receptor [22], interleukin-1 [19], matrix metalloproteinase-3(MMP-3) [20], tissue inhibitor of metalloproteinase-1(TIMP-1) [21], and cyclooxygenase-2 [21].…”

Parameters of Nuclear Magnetic Resonance in Patients With Congenital Narrowing of the Lumbar Spinal Canal

“…3,4,5 These findings suggest that there is a genetic predisposition similar to that which occurs in intervertebral disc degnenraiton. 6,7 In a 2009 study by Kalichman et al, 8 the prevalence of congenital and acquired lumbar stenosis was evaluated radiographically in 191 individuals, averaging 52.6 years of age and with an average BMI of 27.8, who had suffered at least one month of low back pain within a one year timeframe.…”