Association of a single nucleotide polymorphism in the WISP1 gene with spinal osteoarthritis in postmenopausal Japanese women.
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.
Urano
Tomohiko
T
Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Narusawa
Ken'ichiro
K
Shiraki
Masataka
M
Usui
Takahiko
T
Sasaki
Noriko
N
Hosoi
Takayuki
T
Ouchi
Yasuyoshi
Y
Nakamura
Toshitaka
T
Inoue
Satoshi
S
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
D055511:CCN Intercellular Signaling Proteins; C116396:CCN4 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins