163 Persistent MRSA bacteremia 8 Figure 1. Proposed relationship of DNMT3A polymorphisms and increased risk of persistent MRSAB. Created using Biorender. Host genetic variation and persistent MRSAB Despite the advances in our understanding of genetic risk factors for SAB, none of these studies addressed which genetic variants protect or place patients at risk of persistent methicillin-susceptible or methicillin-resistant SAB. A breakthrough discovery was made by Mba Medie et al., who identified a key association between genetic variation in the DNMT3A gene and protection against persistent MRSAB [46]. This elegant study performed whole-exome sequencing (WES) on a cohort of 68 patients with persistent MRSAB (n = 34), defined as persistently positive blood cultures for ≥5 days, and resolving MRSAB (n = 34), defined as blood culture positivity for <5 days. These patients were matched by sex, age, race, presence of implanted devices, diabetes mellitus status, and hemodialysis status. The study revealed a specific polymorphism (g.25498283A > C) in the DNA methyltransferase 3A intronic region of DNMT3A that was associated with a reduced risk of persistent MRSAB. The variant was identified in 61.8% of the cohort with resolving bacteremia and just 8.8% of patients with persistent bacteremia (p = 7.8 × 10-6). Examination of the DNA methylation patterns between patients with and without the g.25498283A > C
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