ArticleProceedings of the National Academy of Sciences of the United States of America2004
Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers, 6 of them syntheses that pooled it.
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Who cites it
152 citing papers in PubMed, 6 syntheses or guidelines pooled it, 396 citations in OpenAlex.
- Genetic effects of rs3740199 polymorphism in ADAM12 gene on knee osteoarthritis: a meta-analysis.Journal of orthopaedic surgery and research · 2017Pooled it
- A comprehensive meta-analysis of association between genetic variants of GDF5 and osteoarthritis of the knee, hip and hand.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2015Pooled it
- Large-scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand.Arthritis and rheumatism · 2009Pooled it
- Hip pain and mobility deficits--hip osteoarthritis: clinical practice guidelines linked to the international classification of functioning, disability, and health from the orthopaedic section of the American Physical Therapy Association.The Journal of orthopaedic and sports physical therapy · 2009Guideline
- Osteoarthritis susceptibility loci defined by genome scan meta-analysis.Rheumatology international · 2006Pooled it
- Osteoarthritis susceptibility loci defined by genome scan meta-analysis.Rheumatology international · 2006Pooled it
- Lorecivivint, a Novel Intraarticular CDC-like Kinase 2 and Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitor and Wnt Pathway Modulator for the Treatment of Knee Osteoarthritis: A Phase II Randomized Trial.Arthritis & rheumatology (Hoboken, N.J.) · 2020Trial
- Single-Cell Transcriptomic Profiling Reveals Superficial Zone Chondrocytes as a Catabolic and Senescent Focus in Osteoarthritis Cartilage.Cartilage · 2026Article
- Review
- Osteochondrosis in horses: An overview of genetic and other factors.Equine veterinary journal · 2026Review
- Connections Between Gene Polymorphism and Fetlock and Hock Measurements in Polish Sport Horses.International journal of molecular sciences · 2025Article
- Genetics of morphological hip abnormalities and their implications for osteoarthritis: a scoping review.Journal of hip preservation surgery · 2025Review
- Targeting the Wnt pathway for the treatment of Osteoarthritis of the knee.Seminars in arthritis and rheumatism · 2025Article
- HAMA-SBMA hydrogel with anti-inflammatory properties delivers cartilage organoids, boosting cartilage regeneration.Journal of nanobiotechnology · 2025Article
- Loosening the Lid on Shoulder Osteoarthritis: How the Transcriptome and Metabolic Syndrome Correlate with End-Stage Disease.International journal of molecular sciences · 2025Article
- Development of novel osteoarthritis therapy by targeting AMPK-β-catenin-Runx2 signaling.Genes & diseases · 2025Review
- IGF1 drives Wnt-induced joint damage and is a potential therapeutic target for osteoarthritis.Nature communications · 2024Article
- Article
- Conditioned Medium From Stem Cells of Human Exfoliated Deciduous Teeth Alleviates Mouse Osteoarthritis by Inducing sFRP1-Expressing M2 Macrophages.Stem cells translational medicine · 2024Article
- Article
92 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoarthritis (OA) is a leading cause of disability in Western society with multiple risk factors, including a complex genetic pattern. Identifying loci involved in the heredity of OA might lead to insights into the molecular pathogenesis of this common disorder. A previous genome scan mapped a primary hip OA susceptibility locus to chromosome 2q with a maximum multipoint logarithm of odds score of 1.6 in 378 affected sibling pair families. Here, microsatellite targeting of eight candidate genes in this region from 2q23-2q32 demonstrated significant associations with the tumor necrosis factor alpha-induced protein 6 gene in all probands and the integrin alpha 6 and frizzled motif associated with bone development (FRZB) genes in female probands. However, genotyping showed lack of association for a nonsynonymous single-nucleotide polymorphism in tumor necrosis factor alpha-induced protein 6, whereas a single-nucleotide polymorphism in FRZB resulting in an Arg324Gly substitution at the carboxyl terminus was associated with hip OA in the female probands (P = 0.04). This association was confirmed in an independent cohort of female hip cases (n = 338; P = 0.04). In addition, a haplotype coding for substitutions of two highly conserved arginine residues (Arg200Trp and Arg324Gly) in FRZB was a strong risk factor for primary hip OA, with an odds ratio of 4.1 (P = 0.004). FRZB encodes secreted frizzled-related protein 3, which is a soluble antagonist of wingless (wnt) signaling. Variant secreted frizzled-related protein 3 with the Arg324Gly substitution had diminished ability to antagonize wnt signaling in vitro. Hence, functional polymorphisms within FRZB confer susceptibility for hip OA in females and implicate the wnt signaling pathway in the pathogenesis of this disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.