Abstract
The NF-κB pathway is involved in the pathogenesis of neurological disorders that have inflammation as a hallmark, including Parkinson’s disease (PD). Our objective was to determine whether common functional variants in the NFKB1, NFKBIA and NFKBIZ genes were associated with the risk of PD. A total of 532 Spanish PD cases (61% male; 38% early-onset, ≤ 55 years) and 300 population controls (50% ≤55 years) were genotyped for the NFKB1 rs28362491 and rs7667496, NFKBIA rs696, and NFKBIZ rs1398608 polymorphisms. We compared allele and genotype frequencies between early and late-onset, male and female, and patient’s vs. controls. We found that the two NFKB1 alleles were significantly associated with PD in our population (p = 0.01; total patients vs. controls), without difference between Early and Late onset patients. The frequencies of the NFKB1 variants significantly differ between male and female patients. Compared to controls, male patients showed a significantly higher frequency of rs28362491 II (p = 0.02, OR = 1.52, 95%CI = 1.10–2.08) and rs28362491 C (p = 0.003, OR = 1.62, 95%CI = 1.18–2.22). The two NFKB1 variants were in strong linkage disequilibrium and the I-C haplotype was significantly associated with the risk of PD among male (p = 0.002). In conclusion, common variants in the NF-kB genes were associated with the risk of developing PD in our population, with significant differences between male and female. These results encourage further studies to determine the involvement of the NF-kB components in the pathogenesis of Parkinson´s disease.
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The data that support the findings of this study are available from the corresponding author upon reasonable request. An Excel file with the raw data would be available for meta-analysis research.
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Acknowledgements
This study has been funded by Instituto de Salud Carlos III (ISCIII) through the project P21/0467 and co-funded by the European Union. S.P.O. is supported by a predoctoral grant from FINBA. D.V.C. is supported by Fundación Parkinson Asturias-Obra Social Cajastur.
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All the authors contributed to this work by recruiting the patients and controls (MBE, MMG, PS, ES, CGF, BCF), performing the genetic study (SPO, DVC, SP, EC, VA), and/or the statistical analysis (EC, VA). E.C. and V.A. wrote the ms. All the authors have revised the text and approved the submission.
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This study was approved by the clinical research ethics committee of Hospital Universitario Central Asturias (HUCA). All the participants gave written or verbal consent. Data were handled in observance of Spanish legislation on data protection. The study complies with the principles of the Declaration of Helsinki (“Recommendations guiding doctors in biomedical research involving human subjects”).
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Perez-Oliveira, S., Vazquez-Coto, D., Pardo, S. et al. NFKB1 variants were associated with the risk of Parkinson´s disease in male. J Neural Transm (2024). https://doi.org/10.1007/s00702-024-02759-1
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DOI: https://doi.org/10.1007/s00702-024-02759-1