Higher Promoter Methylation of the Ubiquitin-Associated and SH3 Domain Containing A (UBASH3A) Gene Is Associated With T-Lymphocyte Ontogeny and Reduced Susceptibility to Early-Onset Sepsis.
cross_sectional · Level IV
Where this comes from
- Record sourced from PubMed, PMID 41408597.
- Also identified by DOI 10.1093/infdis/jiaf636 and PMC identifier 13017222.
- Licence recorded as CC BY-NC-ND.
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Abstract
We investigated the genetic and epigenetic regulation of the UBASH3A gene and its association with early-onset sepsis. Using matched whole blood DNA methylation, gene expression, genotypes, and immune cell counts from the EPIC-HIPC newborn cohort, we report that promoter methylation was negatively correlated (Pearson r = -0.5, P < 2.2 × 10-16) with ontogenetic changes in UBASH3A gene expression and circulating CD3+ T-cell numbers. Higher promoter methylation at birth was associated with lower UBASH3A expression and reduced early-onset sepsis risk (odds ratio, 0.26; P = .015). Genetic variation significantly influenced variations in baseline UBASH3A methylation (132 cis-meQTL, false discovery rate <0.05).
Medical subject headings
- DNA Methylation
- Genetic Predisposition to Disease
- T-Lymphocytes
- Promoter Regions, Genetic
- Adaptor Proteins, Signal Transducing
- Sepsis