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.

Wang, Ziyi; Amenyogbe, Nelly; Ben-Othman, Rym; Cai, Bing; Lo, Mandy; Idoko, Olubukola T; Odumade, Oludare A; Falsafi, Reza et al. · J Infect Dis · 2026

cross_sectional · Level IV

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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).

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