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Ancestral contribution of the muscle-specific creatine kinase (CKM) polymorphism rs4884 in the knee osteoarthritis risk: a preliminary study

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Abstract

Introduction/Objectives

Articular cartilage and periarticular muscle tissues are strongly affected during knee osteoarthritis (OA). Creatine kinase (CK) is an enzyme expressed in several tissues, but the isoform CK-MM is specific of skeletal muscle, and its serum concentration is used as a biomarker of muscle damage. Genetic variants of the CKM gene have been associated with various pathologies, but to date, there are no reports of association with OA. Due to the rs4884 polymorphism being well represented in the Mexican population, it is used as an ancestry informative marker; thus, the goal of this preliminary report was to evaluate the association of this polymorphism in primary knee OA Mexican patients.

Method

Eighty-seven patients with primary knee OA were compared with 107 healthy controls. Serum CK-MM was determined using the dot blot system, and genotyping was performed using the OpenArray system. Logistic regression models were used to assess the association between the rs4884 polymorphism and OA susceptibility adjusting by gender, age, and body mass index.

Results

There were no significant differences in serum CK-MM values between patients and controls. The GG genotype and the G allele had a higher frequency in the control group compared with the OA group (24.3% vs. 12.6%, OR = 0.34, 95% CI = 0.14–0.84, P = 0.019; and 40.2% vs. 28.2%, OR = 0.51, 95% CI = 0.32–0.82, P = 0.005, respectively).

Conclusions

Our results suggest a protection role of the rs4884 polymorphism against knee OA development; further studies are required to confirm it.

Key Points

• CK-MM enzyme catalyzes the conversion of creatine and ATP to create phosphocreatine and ADP; this reaction is reversible.

• In tissues that consume ATP rapidly, such as skeletal muscle, the phosphocreatine serves as an important energy reservoir.

• During knee OA, peripheral muscle tissues of the joint may be affected.

• The rs4884 polymorphism of the CKM gene may participate as a protective factor in the development of OA.

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Acknowledgments

This work was supported by federal resources from the INR-LGII.

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Authors and Affiliations

  1. Synovial Fluid Laboratory, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Calzada México-Xochimilco 289, Colonia Arenal de Guadalupe, Tlalpan, 14389, Mexico City, Mexico

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

  2. Biology Department, Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Coyoacán, 04510, Mexico City, Mexico

    Javier Fernández-Torres

  3. Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados (CINVESTAV) del Instituto Politécnico Nacional, Av. IPN #2508, Colonia San Pedro Zacatenco, 07360, Gustavo A Madero, CP 07360, Mexico City, Mexico

    Olivier Christophe Barbier & Juana Narváez-Morales

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  1. Javier Fernández-Torres
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  2. Gabriela Angélica Martínez-Nava
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Correspondence to Karina Martínez-Flores.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the INR-LGII-Institutional Research and with the Helsinki declaration (1964). Informed consent was obtained from all individual participants included in the study.

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Fernández-Torres, J., Martínez-Nava, G.A., Zamudio-Cuevas, Y. et al. Ancestral contribution of the muscle-specific creatine kinase (CKM) polymorphism rs4884 in the knee osteoarthritis risk: a preliminary study. Clin Rheumatol 40, 279–285 (2021). https://doi.org/10.1007/s10067-020-05238-6

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  • DOI: https://doi.org/10.1007/s10067-020-05238-6

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