title: Association of a single nucleotide polymorphism in the WISP1 gene with spinal osteoarthritis in postmenopausal Japanese women.
abstract: The Wnt-beta-catenin signaling pathway that regulates bone density is also involved in cartilage development and homeostasis in vivo. Here, we assumed that genetic variation in Wnt-beta-catenin signaling genes can affect the pathogenesis of cartilage related diseases, such as osteoarthritis. Wnt-1-induced secreted protein 1 (WISP1) is a target of the Wnt pathway and directly regulated by beta-catenin. In the present study, we analyzed the association of a single nucleotide polymorphism (SNP) in the WISP1 3'-UTR region with the development of radiographically observable osteoarthritis of the spine. For this purpose, we evaluated the presence of osteophytes, endplate sclerosis, and narrowing of disc spaces in 304 postmenopausal Japanese women. We compared those who carried the G allele (GG or GA, n = 184) with those who did not (AA, n = 120). We found that the subjects without the G allele (AA) were significantly over-represented in the subjects having higher endplate sclerosis score (P = 0.0069; odds ratio, 2.91; 95% confidence interval, 1.34-6.30 by logistic regression analysis). On the other hand, the occurrence of disc narrowing and osteophyte formation did not significantly differ between those with and without at least one G allele. Thus, we suggest that a genetic variation in the WISP1 gene locus is associated with spinal osteoarthritis, in line with the involvement of the Wnt-beta-catenin-regulated gene in bone and cartilage metabolism.
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Urano
authors.forename: Ken'ichiro
authors.initials: K
authors.lastname: Narusawa
authors.forename: Masataka
authors.initials: M
authors.lastname: Shiraki
authors.forename: Takahiko
authors.initials: T
authors.lastname: Usui
authors.forename: Noriko
authors.initials: N
authors.lastname: Sasaki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Hosoi
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Ouchi
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nakamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
mesh_terms: D000368:Aged; D055511:CCN Intercellular Signaling Proteins; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007564:Japan; D010003:Osteoarthritis / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013166:Spondylitis / Q000235:genetics* / Q000473:pathology
chemical_list: D055511:CCN Intercellular Signaling Proteins; C116396:CCN4 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins