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The interplay between HLA-B and NLRP3 polymorphisms may be associated with the genetic susceptibility of gout

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Abstract

Background

HLA and NLRP3 play an important role in the development of various autoimmune and autoinflammatory diseases. Gout is an autoinflammatory disease associated with multiple genetic and environmental factors. The objective of the present study was to evaluate the interaction and association between genetic polymorphisms of HLA-B and the NLRP3 gene in Mexican patients with gout.

Methods and results

Eighty-one patients with gout were included and compared with 95 healthy subjects. The polymorphisms rs4349859, rs116488202, rs2734583 and rs3099844 (within the HLA-B region) and rs3806268 and rs10754558 of the NLRP3 gene were genotyped using TaqMan probes in a Rotor-Gene device. The interactions were determined using the multifactorial dimensionality reduction (MDR) method, while the associations were determined through logistic regression models. The MDR analysis revealed significant interactions between the rs116488202 and rs10754558 polymorphisms with an entropy value of 4.31% (p < 0.0001). Significant risk associations were observed with rs4349859 and rs116488202 polymorphisms (p < 0.01); however, no significant associations were observed with the polymorphisms of the NLRP3 gene.

Conclusions

The results suggest that HLA-B polymorphisms and their interaction with NLRP3 may contribute to the genetic susceptibility of gout.

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Data availability

The data that support the findings of this study are available on request from the corresponding author.

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Acknowledgements

This work was supported by federal resources from the INR-LGII. We thank all the individuals who participated in this study. We thank Dr. Ambar López-Macay for providing us his Rotor-Gene Q real-time thermal cycler for genotyping.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Laboratorio de Líquido Sinovial, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico

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

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

    Javier Fernández-Torres

  3. Laboratorio de Gerociencias, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico

    Gabriela Angélica Martínez-Nava

  4. Unidad de Ingeniería de Tejidos, Terapia Celular y Medicina Regenerativa, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico

    Roberto Sánchez-Sánchez

  5. Rheumatology Division, Instituto Nacional de Rehabilitación “Luis Guillermo Ibarra Ibarra”, Mexico City, Mexico

    Luis J. Jara

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  1. Javier Fernández-Torres
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Contributions

JF-T, YZ-C: Concept and design. JF-T, GAM-N, KM-F, RS-S, LJJ-Q, YZ-C: Experiments and procedures. JF-T, YZ-C, KM-F: Writing of article. JF-T, GAM-N: Statistical analysis. GAM-N, KM-F, RS-S, LJJ-Q: Patient selection. All authors reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to Yessica Zamudio-Cuevas.

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This study was approved by the Ethics and Research Committee 20 CI 09 013 029 of the Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra (registration number INR-07/22). All procedures performed in this study involving human participants were in accordance with the ethical standards of the INR-LGII-Institutional Research and Ethical Committee 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., Martínez-Flores, K. et al. The interplay between HLA-B and NLRP3 polymorphisms may be associated with the genetic susceptibility of gout. Mol Biol Rep 49, 10205–10215 (2022). https://doi.org/10.1007/s11033-022-07895-z

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