Abstract
The aim of this study was to investigate whether the alpha 2 type IX collagen (COL9A2) polymorphism that introduces tryptophan residue into the collagen triple-helix is a marker of susceptibility to, or severity of, rheumatoid arthritis (RA). The study included 749 Japanese patients with RA. One hundred twenty-four unrelated healthy individuals served as the control subjects. The relationship between the COL9A2 gene polymorphism and clinical manifestations of RA was evaluated. For the number of subjects positive for COL9A2 tryptophan polymorphism, there was no statistically significant difference between RA patients and normal controls. Furthermore, we did not detect any association of COL9A2 tryptophan polymorphism with disease status, least erosive subset, more erosive subset, or mutilating disease. The lack of association of COL9A2 tryptophan polymorphism with RA and the clinical findings in our study implies that the polymorphism may not function as a candidate gene marker for screening RA patients.
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References
Symmons D, Turner G, Webb R, Asten P, Barrett E, Lunt M, Scott D, Silman A (2002) The prevalence of rheumatoid arthritis in the United Kingdom: new estimates for a new century. Rheumatology (Oxford) 41:793–800
Barton A, Ollier W (2002) Genetic approaches to the investigation of rheumatoid arthritis. Curr Opin Rheumatol 14:260–269
Eyre D (2002) Collagen of articular cartilage. Arthritis Res 4:30–35
Muragaki Y, Mariman EC, van Beersum SE, Perala M, van Mourik JB, Warman ML, Hamel BC, Olsen BR (1996) A mutation in COL9A2 causes multiple epiphyseal dysplasia (EDM2). Ann N Y Acad Sci 785:303–306
Kimura T, Nakata K, Tsumaki N, Miyamoto S, Matsui Y, Ebara S, Ochi T (1996) Progressive degeneration of articular cartilage and intervertebral discs. A experimental study in transgenic mice bearing a type IX collagen mutation. Int Orthop 20:177–181
Nakata K, Ono K, Miyazaki J, Olsen BR, Muragaki Y, Adachi E, Yamamura K, Kimura T (1993) Osteoarthritis associated with mild chondrodysplasia in transgenic mice expressing alpha 1(IX) collagen chains with a central deletion. Proc Natl Acad Sci U S A 90:2870–2874
Paassilta P, Lohiniva J, Goring HH, Perala M, Raina SS, Karppinen J, Hakala M, Palm T, Kroger H, Kaitila I, Vanharanta H, Ott J, Ala-Kokko L (2001) Identification of a novel common genetic risk factor for lumbar disk disease. JAMA 285:1843–1849
Annunen S, Paassilta P, Lohiniva J, Perala M, Pihlajamaa T, Karppinen J, Tervonen O, Kroger H, Lahde S, Vanharanta H, Ryhanen L, Goring HH, Ott J, Prockop DJ, Ala-Kokko L (1999) An allele of COL9A2 associated with intervertebral disc disease. Science 285:409–412
Matsui Y, Mirza SK, Wu JJ, Carter B, Bellabarba C, Shaffrey CI, Chapman JR, Eyre DR (2004) The association of lumbar spondylolisthesis with collagen IX tryptophan alleles. J Bone Joint Surg Br 86:1021–1026
Ikeda T, Mabuchi A, Fukuda A, Kawakami A, Ryo Y, Yamamoto S, Miyoshi K, Haga N, Hiraoka H, Takatori Y, Kawaguchi H, Nakamura K, Ikegawa S (2002) Association analysis of single nucleotide polymorphisms in cartilage-specific collagen genes with knee and hip osteoarthritis in the Japanese population. J Bone Miner Res 17:1290–1296
Hamada D, Takata Y, Osabe D, Nomura K, Shinohara S, Egawa H, Nakano S, Shinomiya F, Scafe CR, Reeve VM, Miyamoto T, Moritani M, Kunika K, Inoue H, Yasui N, Itakura M (2005) SNPs in the SEC8L1 gene, encoding a subunit of the exocyst complex, are associated with rheumatoid arthritis in Japanese population. Arthritis Rheum 52:1371–1380
Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324
Ochi T, Iwase R, Yonemasu K, Matsukawa M, Yoneda M, Yukioka M, Ono K (1988) Natural course of joint destruction and fluctuation of serum C1q levels in patients with rheumatoid arthritis. Arthritis Rheum 31:37–43
Pihlajamaa T, Vuoristo MM, Annunen S, Perala M, Prockop DJ, Ala-Kokko L (1998) Human COL9A1 and COL9A2 genes. Two genes of 90 and 15 kb code for similar polypeptides of the same collagen molecule. Matrix Biol 17:237–241
Matsui Y, Wu JJ, Weis MA, Pietka T, Eyre DR (2003) Matrix deposition of tryptophan-containing allelic variants of type IX collagen in developing human cartilage. Matrix Biol 22:123–129
Wu JJ, Eyre DR (2003) Intervertebral disc collagen. Usage of the short form of the alpha1(IX) chain in bovine nucleus pulposus. J Biol Chem 278:24521–24525
Acknowledgements
We are grateful to the patients with RA and the controls for participation in this study. This work was supported by grants from the Japan Rheumatism Foundation, the Japan Society for the Promotion of Science (grant no. 16591496), the Japan Orthopaedics and Traumatology Foundation (grant no. 0142), and the Nakatomi Foundation.
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Takata, Y., Matsui, Y., Hamada, D. et al. The alpha 2 type IX collagen gene tryptophan polymorphism is not associated with rheumatoid arthritis in the Japanese population. Clin Rheumatol 25, 491–494 (2006). https://doi.org/10.1007/s10067-005-0067-3
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DOI: https://doi.org/10.1007/s10067-005-0067-3