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Impact of the gene-gene interactions related to the HIF-1α signaling pathway with the knee osteoarthritis development

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Abstract

Introduction/objectives

Articular cartilage is the target tissue of osteoarthritis (OA), and because it lacks capillary networks, the microenvironment is hypoxic. Hypoxia inducible factor-1 alpha (HIF-1α) regulates the homeostasis of this tissue. The aim of this study was to investigate whether genetic polymorphisms of the HIF-1α signaling pathway are involved in the development of knee OA.

Method

We performed a case-control association study and genotyped 134 knee OA patients and 267 healthy controls. All participants were genotyped in order to evaluate 42 SNPs from 22 genes involved in the HIF-1α signaling pathway using the OpenArray technology. Gene-gene interactions (epistasis) were analyzed using the multifactor dimensionality reduction (MDR) method.

Results

The MDR analysis showed epistasis between AKT2 (rs8100018) and IGF1 (rs2288377), AKT2 (rs8100018) and IGF1 (rs35767), IGF1 (rs35767) and COL2A1 (rs1793953), and between GSK3B (rs6438552) and IGF1 (rs35767) polymorphisms, with information gain values of 21.24%, 8.37%, 9.93%, and 5.73%, respectively. Additionally, our model allowed us to identify high- and low-risk genotypes among COL2A1 rs1793953, GSK3B rs6438552, AKT2 rs8100018, and IGF1 rs35767 polymorphisms.

Conclusions

Knowing the interactions of these polymorphisms involved in HIF-1α signaling pathway could provide a new diagnostic support tool to identify individuals at high risk of developing knee OA.

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Acknowledgements

We thank the support provided by Dr. Gustavo Reyes Terán in facilitating the laboratory where we genotyped the samples.

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Authors and Affiliations

  1. Synovial Fluid Laboratory, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico

    Javier Fernández-Torres, Gabriela Angélica Martínez-Nava, Yessica Zamudio-Cuevas, Karina Martínez-Flores & Alberto López-Reyes

  2. Biological and Health Sciences PhD Program, Universidad Autónoma Metropolitana Iztapalapa, Mexico City, Mexico

    Javier Fernández-Torres

  3. Health Sciences Department, Universidad Autónoma Metropolitana Iztapalapa, Mexico City, Mexico

    María Concepción Gutiérrez-Ruíz & Luis Enrique Gómez-Quiroz

  4. Center for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, Mexico

    Daniela Garrido-Rodríguez

  5. Departamento de Biología Molecular y Genómica, Instituto de Investigación en Ciencias Biomédicas (IICB), Universidad de Guadalajara, Guadalajara, Mexico

    José Francisco Muñoz-Valle & Edith Oregón-Romero

  6. Rheumatology Service, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico

    Carlos Lozada

  7. Musculoskeletal and Rheumatic Diseases Division, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico

    Denise Clavijo Cornejo & Carlos Pineda

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  1. Javier Fernández-Torres
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  2. Gabriela Angélica Martínez-Nava
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  7. Daniela Garrido-Rodríguez
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  8. José Francisco Muñoz-Valle
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  11. Denise Clavijo Cornejo
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  12. Carlos Pineda
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  13. Alberto López-Reyes
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Corresponding author

Correspondence to Alberto López-Reyes.

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Written informed consent was obtained from all participants according to the Declaration of Helsinki and the study protocol was approved by ethics committee of the National Research Centre.

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Fernández-Torres, J., Martínez-Nava, G.A., Zamudio-Cuevas, Y. et al. Impact of the gene-gene interactions related to the HIF-1α signaling pathway with the knee osteoarthritis development. Clin Rheumatol 38, 2897–2907 (2019). https://doi.org/10.1007/s10067-019-04635-w

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  • DOI: https://doi.org/10.1007/s10067-019-04635-w

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