Mediating and moderating effects of plasma proteomic biomarkers on the association between poor oral health problems and brain white matter microstructural integrity: the UK Biobank study.

Autor: Beydoun MA; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA. baydounm@mail.nih.gov., Beydoun HA; VA National Center on Homelessness Among Veterans, U.S. Department of Veterans Affairs, Washington, DC, 20420, USA.; Department of Management, Policy, and Community Health, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA., Hu YH; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA., Li Z; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA., Georgescu MF; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA., Noren Hooten N; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA., Bouhrara M; Laboratory of Clinical Investigation, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA., Weiss J; Stanford Center on Longevity, Stanford University, Stanford, CA, 94301, USA., Launer LJ; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA., Evans MK; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA., Zonderman AB; Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, Baltimore, MD, 21224, USA.
Jazyk: angličtina
Zdroj: Molecular psychiatry [Mol Psychiatry] 2024 Jul 30. Date of Electronic Publication: 2024 Jul 30.
DOI: 10.1038/s41380-024-02678-3
Abstrakt: The plasma proteome can mediate associations between periodontal disease (Pd) and brain white matter integrity (WMI). We screened 5089 UK Biobank participants aged 40-70 years for poor oral health problems (POHP). We examined the association between POHP and WMI (fractional anisotropy (FA), mean diffusivity (MD), Intracellular Volume Fraction (ICVF), Isotropic Volume Fraction (ISOVF) and Orientation Diffusion (OD)), decomposing the total effect through the plasma proteome of 1463 proteins into pure mediation, pure interaction, neither, while adjusting for socio-demographic and cardiovascular health factors. Similarly, structural equations modeling (SEM) was conducted. POHP was more prevalent among men (12.3% vs. 9.6%), and was associated with lower WMI on most metrics, in a sex-specific manner. Of 15 proteins strongly associated with POHP, growth differentiation factor 15 (GDF15) and WAP four-disulfide core domain 2 (WFDC2; also known as human epididymis protein 4; HE4) were consistent mediators. Both proteins mediated 7-8% of total POHP effect on FA mean . SEM yielded significant total effects for FA mean , MD mean and ISOVF mean in full models, with %mediated by common latent factor (GDF15 and WFDC2) ranging between 13% (FA mean ) and 19% (ISOVF mean ). For FA, mediation by this common factor was found for 16 of 49 tract-specific and global mean metrics. Protein metabolism, immune system, and signal transduction were the most common pathways for mediational effects. POHP was associated with poorer WMI, which was partially mediated by GDF15 and WFDC2.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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