Sex-specific epigenetic signatures of circulating urate and its increase after BCG vaccination.

Autor:	Liu Z; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany.; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany., Crișan TO; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center. Nijmegen, the Netherlands.; Department of Medical Genetics, 'Iuliu Hațieganu' University of Medicine and Pharmacy. Cluj-Napoca, Romania., Qi C; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany.; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany., Gupta MK; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany.; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany., Liu X; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany.; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany., Moorlag SJCFM; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center. Nijmegen, the Netherlands., Koeken VACM; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany.; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany.; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center. Nijmegen, the Netherlands.; Research Centre Innovations in Care, Rotterdam University of Applied Sciences, Rotterdam, the Netherlands., de Bree LCJ; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center. Nijmegen, the Netherlands., Mourits VP; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center. Nijmegen, the Netherlands., Gao X; Department of Environmental Health, Mailman School of Public Health, Columbia University, New York, NY, USA.; Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing, China., Baccarelli A; Department of Environmental Health, Mailman School of Public Health, Columbia University, New York, NY, USA.; Harvard T.H. Chan School of Public Health, Boston, MA, USA., Schwartz J; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Pessler F; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany.; Research Group Biomarkers for Infectious Diseases, TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany., Guzmán CA; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany.; Department Vaccinology and Applied Microbiology, Helmholtz-Centre for Infection Research (HZI), Braunschweig, Germany., Li Y; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany.; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany.; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center. Nijmegen, the Netherlands.; Cluster of Excellence RESIST (EXC 2155), Hanover Medical School, Hannover, Germany.; Lower Saxony center for artificial intelligence and causal methods in medicine (CAIMed). Hannover, Germany., Netea MG; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center. Nijmegen, the Netherlands.; Department for Immunology and Metabolism, Life and Medical Sciences Institute (LIMES). University of Bonn. Bonn, Germany., Joosten LAB; Department of Internal Medicine and Radboud Center for Infectious Diseases (RCI), Radboud University Medical Center. Nijmegen, the Netherlands.; Department of Medical Genetics, 'Iuliu Hațieganu' University of Medicine and Pharmacy. Cluj-Napoca, Romania., Xu CJ; Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany.; TWINCORE, a joint venture between the Helmholtz-Centre for Infection Research (HZI) and Hannover Medical School (MHH). Hannover, Germany.
Jazyk:	angličtina
Zdroj:	Research square [Res Sq] 2024 Jul 22. Date of Electronic Publication: 2024 Jul 22.
DOI:	10.21203/rs.3.rs-4498597/v1
Abstrakt:	Background: Urate concentration and the physiological regulation of urate homeostasis exhibit clear sex differences. DNA methylation has been shown to explain a substantial proportion of serum urate variance, mediate the genetic effect on urate concentration, and co-regulate with cardiometabolic traits. However, whether urate concentration is associated with DNA methylation in a sex-dependent manner is unknown. Additionally, it is worth investigating if urate changes after perturbations, such as vaccination, are associated with DNA methylation in a sex-specific manner. Methods: We investigated the association between DNA methylation and serum urate concentrations in a Dutch cohort of 325 healthy individuals. Urate concentration and DNA methylation were measured before and after Bacillus Calmette-Guérin (BCG) vaccination, used as a perturbation associated with increased gout flares. The association analysis included united, interaction, and sex-stratified analysis. Validation of the identified CpG sites was conducted using three independent cohorts. Results: 215 CpG sites were associated with serum urate in males, while 5 CpG sites were associated with serum urate in females, indicating sex-specific associations. Circulating urate concentrations significantly increased after BCG vaccination, and baseline DNA methylation was associated with differences in urate concentration before and after vaccination in a sex-specific manner. The CpG sites associated with urate concentration in males were enriched in neuro-protection pathways, whereas in females, the urate change-associated CpG sites were related to lipid and glucose metabolism. Conclusion: Our study enhances the understanding of how epigenetic factors contribute to regulating serum urate levels in a sex-specific manner. These insights have significant implications for the diagnosis, prevention, and treatment of various urate-related diseases and highlight the importance of personalized and sex-specific approaches in medicine. Competing Interests: Additional Declarations: There is NO Competing Interest.
Databáze:	MEDLINE
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