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.

Association of polymorphisms of SORBS1, GCK and WISP1 with hypertension in community-dwelling Japanese individuals

“…37 The 2364A-G polymorphism was shown to be related to spinal osteoarthritis in postmenopausal Japanese women, with the G allele protecting against this condition. 15 The 2364A-G polymorphism (rs2929970) is located in the 3¢-untranslated region of WISP1. An LD block containing this polymorphism includes B5.5 kb from intron 3 to 3¢ region of the gene.…”

The Role of Synovial Macrophages and Macrophage-Produced Mediators in Driving Inflammatory and Destructive Responses in Osteoarthritis

“…During experimental OA wnt-signalling is not only occurring in the cartilage but also in the synovium, as was found by -catenin staining. WISP-1, a gene in which a polymorphism was shown to be associated with spinal OA (Urano et al, 2007) was strongly upregulated in the synovium of two models for OA. Further investigation indicated that WISP-1 is a potent inducer of MMPs in macrophages, whereas the short term effect on chondrocytes is less pronounced.…”

Single-nucleotide polymorphism in the hyaluronan and proteoglycan link protein 1 (HAPLN1) gene is associated with spinal osteophyte formation and disc degeneration in Japanese women

“…Attempting to elucidate the pathogenesis of lower back pain, we previously investigated the association of various genetic factors with spinal degeneration [23][24][25][26]. In our previous studies on the common genetic variants associated with spinal degeneration, we found that polymorphism of the LRP5 gene correlated with osteophyte formation [26], while that of the IGF1R correlated with disc space narrowing [25].…”

“…Both lateral projections in the lateral decubitus position and A-P projections in the supine position were obtained at a constant focus-film distance of 1.5 m. The severity of spinal degeneration, including osteophyte formation, endplate sclerosis, and disc space narrowing, was semiquantitatively assessed from the T4/5 to L4/5 disc level or from the T4 to L4 level using the grading scale described by Genant [31]. Next, we radiographically assessed spinal disc degeneration by using a previously reported scoring system [23][24][25][26]. In brief, osteophyte formation at a particular disc level was graded 0-3 degrees; endplate sclerosis, 0-2 degrees; disc space narrowing, 0-1 degree.…”

“…We identified these four SNPs in the HAPLN1 gene by using the TaqMan (Applied Biosystems) polymerase chain reaction (PCR) method [23][24][25][26]. To identify an SNP in HAPLN1, we used Assays-on-Demand SNP genotyping products, which include sequence-specific forward and reverse primers and two TaqMan MGB probes for detecting alleles.…”