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Wnt-related genes and large-joint osteoarthritis: association study and replication

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Abstract

Osteoarthritis (OA) has a strong genetic component, and experimental evidence suggests the involvement of the Wnt pathway in its pathogenesis. Hence, we explored the association of common single nucleotide polymorphisms (SNPs) related to the Wnt pathway with hip and knee OA. Seventy-eight SNPs were analyzed in 606 patients undergoing joint replacement and in 680 control subjects. SNPs were located in WNT1, WNT10A, WNT16, DVL2, FZD5, BCL9, SFRP1, TCF7L1 and SFRP4 genes. SNPs significantly associated with OA were genotyped in an independent group of 369 patients and 407 controls. One SNP in WNT10A, rs3806557, was associated with hip OA in men (OR 0.65, 95 % CI 0.46–0.93; p = 0.017), but the association was not confirmed in the replication phase. The TCF7L1 polymorphism rs11547160 was also associated with hip OA in the discovery set, but not in the replication set. Similarly, the SFRP4 SNP rs1052981 was associated with knee OA in women with OR of 2.73 (95 % CI 1.29–5.8; p = 0.006), but the association was not replicated. The BCL9 polymorphism rs2353525 was associated with knee OA in women, both in the unadjusted and in the age- and BMI-adjusted analysis (OR 2.01; 95 % CI 1.34–2.98; p = 0.0006). A similar, but not statistically significant, trend was observed in the replication phase. In the combined analysis, OR was 3.13 (1.34–7.28; p = 0.009). These data suggest that some SNPs of genes related to the Wnt pathway and, specifically BCL9, influence the genetic predisposition to osteoarthritis of the large joints in a sex- and joint-specific way.

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Acknowledgments

Supported by a grant from Instituto de Salud Carlos III (FIS 06/0034). We thank María Torres and Angel Carracedo (Centro Nacional de Genotipado), for genotyping the samples. We also thank Carolina Sañudo, Jana Arozamena and Verónica Mijares for their excellent technical assistance.

Conflict of interest

The authors declare that they do not have conflicts of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, Hospital U.M. Valdecilla, IFIMAV, University of Cantabria, Av Valdecilla sn, 39008, Santander, Spain

    Carmen García-Ibarbia, Fernando Ortiz, Javier Velasco & José A. Riancho

  2. Department of Internal Medicine, Hospital U. Río Hortega, University of Valladolid, Valladolid, Spain

    José L. Pérez-Castrillón

  3. Unit of Legal Medicine, University of Cantabria, Santander, Spain

    María T. Zarrabeitia

  4. Department of Orthopedic Surgery, Hospital U.M. Valdecilla, Santander, Spain

    Manuel Sumillera

Authors
  1. Carmen García-Ibarbia
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  2. José L. Pérez-Castrillón
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  3. Fernando Ortiz
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  4. Javier Velasco
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  5. María T. Zarrabeitia
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  6. Manuel Sumillera
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  7. José A. Riancho
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Correspondence to José A. Riancho.

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García-Ibarbia, C., Pérez-Castrillón, J.L., Ortiz, F. et al. Wnt-related genes and large-joint osteoarthritis: association study and replication. Rheumatol Int 33, 2875–2880 (2013). https://doi.org/10.1007/s00296-013-2821-1

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  • DOI: https://doi.org/10.1007/s00296-013-2821-1

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