Epistasis between ADIPOQ rs1501299 and PON1 rs662 polymorphisms is potentially associated with the development of knee osteoarthritis

  • Javier Fernández-TorresEmail author
  • Gabriela Angélica Martínez-Nava
  • Yessica Zamudio-Cuevas
  • Karina Martínez-Flores
  • Rolando Espinosa-Morales
Original Article


Overweight produces oxidative stress (OS) on the articular cartilage, with the subsequent risk of developing knee osteoarthritis (OA). Associations between genetic polymorphisms related to OS and OA have been reported, but it is currently unknown whether there exist interactions among them that affect OA development. To identify and evaluate interactions between multiple SNPs related to OS in Mexican knee OA patients. Ninety-two knee OA patients were included in the study, which were compared to 147 healthy controls. Nine variants of six genes (PEPD, AGER, IL6, ADIPOQ, PON1, and CA6) related to OS were genotyped in both study groups through the OpenArray system. Epistasis was analyzed with the multifactor dimensionality reduction (MDR) method. The MDR analysis revealed a significant interaction (p = 0.0107) between polymorphisms rs1501299 (ADIPOQ) and rs662 (PON1), with an entropy value of 9.84%; in addition, high and low risk genotypes were identified between these two polymorphisms. The effect of the interaction between rs1501299 (ADIPOQ) and rs662 (PON1) polymorphisms seems to play an important role in OA pathogenesis; so the epistasis analysis may provide an excellent tool for identifying individuals at high risk for developing OA.


Knee osteoarthritis Oxidative stress Multifactor dimensionality reduction Epistasis Single nucleotide polymorphism 



We thank the support provided by Dr. Daniela Garrido-Rodríguez in facilitating the laboratory where we genotyped the samples. The authors thank Dr. Alberto López-Reyes for supporting the purchase of the genotyping chip.


The study was funded by departmental resources.

Compliance with ethical standards

Conflict of interest

The authors declare that they have not conflict of interest.

Ethical approval

All procedures performed in this study involving human participants were in accordance with the ethical standards of the INRLGII-Institutional Research and Ethical Committee (CONBIOETICA-09-CEI-031-20171207) and with the Helsinki Declaration (1964). This study was approved by the ethics committee of the INRLGII.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Synovial Fluid LaboratoryInstituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”Mexico CityMexico
  2. 2.Rheumatology DepartmentInstituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”Mexico CityMexico

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