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The association of AKNA gene polymorphisms with knee osteoarthritis suggests the relevance of this immune response regulator in the disease genetic susceptibility

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Abstract

Recent studies have identified AKNA as a potential susceptibility gene for several inflammatory diseases. Here, we aimed to assess the potential association of AKNA polymorphisms with knee osteoarthritis (KOA) susceptibility in a Mexican population, following STREGA recommendations. From a DNA bank of 181 KOA patients and 140 healthy controls, two AKNA SNPs were genotyped using TaqMan probes. The association between KOA susceptibility and AKNA polymorphisms genotypes was evaluated by multivariated logistic regression analysis. Information regarding patients’ inflammatory biomarkers levels was obtained and their association with AKNA polymorphisms genotypes was assessed by lineal regression. We found a positive association with the recessive inheritance model of both AKNA polymorphisms (A/A genotype for both) and KOA susceptibility adjusting by age, body mass index (BMI), gender and place of birth (OR = 2.48, 95% CI 1.09–5.65 for rs10817595 polymorphism; and OR = 4.96; 95% CI 2.421–10.2 for rs3748176 polymorphism). Additionally these associations were also seen after stratifying patients by KOA severity and age. Furthermore the total leukocyte count was positively associated with rs10817595 AKNA polymorphism (β = 1.39; 95% CI 0.44–2.34) adjusting by age, BMI, gender, place of birth and disease severity. We suggest that regulatory and coding polymorphisms of the inflammatory modulator gene AKNA can influence the development of KOA. Further structural and functional studies might reveal the role of AKNA in OA and other rheumatic diseases.

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Acknowledgements

We want to thank Monica Guadalupe Santamaría-Olmedo, Daniel Medina-Luna and Yahir Loissell-Baltazar for their technical assistance; and Cristina Hernández-Díaz MD for reviewing the manuscript.

Funding

The study was funded by departmental resources.

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Authors and Affiliations

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

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

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

    Rolando Espinosa-Morales

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

    Carlos A. Lozada, Marwin Gutierrez & Carlos Pineda

  4. Immunogenetics Division, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”(INCMNSZ), Mexico City, Mexico

    Julio Granados

  5. Chronic Infection and Cancer División, Research Center on Infectious Diseases, Instituto Nacional de Salud Pública, Cuernavaca, Mexico

    Vicente Madrid-Marina

  6. Biological and Health Sciences PhD Program, Universidad Autónoma Metropolitana Iztapalapaa, México City, Mexico

    Javier Fernández-Torres

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  1. Gabriela Angélica Martínez-Nava
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  2. Javier Fernández-Torres
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  3. Karina Martínez-Flores
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  8. Marwin Gutierrez
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  11. Vicente Madrid-Marina
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  12. Alberto López-Reyes
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Correspondence to Alberto López-Reyes.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

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Martínez-Nava, G.A., Fernández-Torres, J., Martínez-Flores, K. et al. The association of AKNA gene polymorphisms with knee osteoarthritis suggests the relevance of this immune response regulator in the disease genetic susceptibility. Mol Biol Rep 45, 151–161 (2018). https://doi.org/10.1007/s11033-018-4148-1

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