Article

A Functional Polymorphism in COL11A1, Which Encodes the α1 Chain of Type XI Collagen, Is Associated with Susceptibility to Lumbar Disc Herniation

Laboratory for Bone and Joint Diseases, School of Medicine, Keio University, Tokyo.
The American Journal of Human Genetics (Impact Factor: 10.99). 12/2007; 81(6):1271-7. DOI: 10.1086/522377
Source: PubMed

ABSTRACT Lumbar disc herniation (LDH), degeneration and herniation of the nucleus pulposus of the intervertebral disc (IVD) of the lumbar spine, is one of the most common musculoskeletal diseases. Its etiology and pathogenesis, however, remain unclear. Type XI collagen is important for cartilage collagen formation and for organization of the extracellular matrix. We identified an association between one of the type XI collagen genes, COL11A1, and LDH in Japanese populations. COL11A1, which encodes the alpha 1 chain of type XI collagen, was highly expressed in IVD, but its expression was decreased in the IVD of patients with LDH. The expression level was inversely correlated with the severity of disc degeneration. A single-nucleotide polymorphism (c.4603C-->T [rs1676486]) had the most significant association with LDH (P=3.3 x 10(-6)), and the transcript containing the disease-associated allele was decreased because of its decreased stability. These observations indicate that type XI collagen is critical for IVD metabolism and that its decrease is related to LDH.

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Available from: Yoshiharu Kawaguchi, Aug 28, 2015
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    • "Association studies of genes encoding for structural and functional components of intervertebral disc have highlighted the participation of polymorphisms in IDD [18, 20– 22], including collagens I [23], IX [24], and XI [25], aggrecan [26], cartilage intermediate layer protein (CILP) [27], ECM-degrading enzymes such as MMP-3 [28] and MMP9, thrombospondin-2 (THBS2) [29], inflammatory cytokines interleukin-1 alpha (IL-1í µí»¼) [30], IL-18 [21], IL-6, and tumor necrosis factor alpha (TNF-í µí»¼) [31], and vitamin D receptor (VDR) [32]. The hormonal form of vitamin D (calcitriol) plays a key role in mineralization of bone, absorption of calcium from the gut, control of calcium and phosphate homeostasis , and regulation of parathyroid hormone secretion and may affect intervertebral disc maintenance by altering the sulfation of glycosaminoglycans as well as other changes relating to the nucleus pulposus ECM. "
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    ABSTRACT: Intervertebral disc degeneration (IDD) is the most common diagnosis in patients with back pain, a leading cause of musculoskeletal disability worldwide. Several conditions, such as occupational activities, gender, age, and obesity, have been associated with IDD. However, the development of this disease has strong genetic determinants. In this study, we explore the possible association between rs1800587 (c.-949C>T) of interleukin-1 alpha (IL1A) and rs2228570 (c.2T>V) and rs731236 (c.1056T>C) of vitamin D receptor (VDR) gene polymorphisms and the development of IDD in northwestern Mexican Mestizo population. Gene polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by age and gender: patients with symptomatic lumbar IDD (n = 100) and subjects with normal lumbar-spine MRI-scans (n = 100). Distribution of the mutated alleles in patients and controls was 27.0% versus 28.0% (P = 0.455) for T of rs1800587 (IL1A); 53.0% versus 58.0% (P = 0.183) for V of rs2228570 (VDR); and 18.0% versus 21.0% (P = 0.262) for C of rs731236 (VDR). Our results showed no association between the studied polymorphisms and IDD in this population. This is the first report on the contribution of gene polymorphisms on IDD in a Mexican population.
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    • "Several previous studies have described the potential gene markers for lumbar disc diseases, including collagen 9A2 [6, 7], vitamin D receptor [8], matrix metalloproteinase (MMP)-3 [9], cartilage intermediate layer protein [10], collagen 11A1 [11], thrombospondin (THBS2) [12], sickle tail (SKT) [13], MMP-9 [12], asporin (ASPN) [14], and carbohydrate sulfotransferase [15]. Systematic reviews demonstrated that there is moderate evidence of correlation of ASPN, COLXIA1, SKT, THBS2, and MMP-9 with HD [16]. "
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    • "Lumbar disc herniation (LDH) and lumbar disc degeneration (LDD) can be viewed as having similar aetiological routes to OA, with each condition being age-associated and involving the degeneration of cartilage, albeit of different types, with OA being hyaline and LDH/LDD being fibrocartilage. The common non-synonymous SNP rs1676486, which is located in exon 62 of COL11A1, has been reported to associate with LDH in a Japanese population [9]. rs1676486 is a C-T transition that results in a proline to serine substitution. "
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