AI Article Synopsis
- Researchers conducted whole genome sequencing on 66 cases of CNS toxicity induced by antimicrobial drugs and 833 controls to explore genetic predispositions.
- The study primarily examined the role of seventeen efflux transporters at the blood-brain barrier and found no significant association, but identified uncommon genetic variants linked to CNS toxicity.
- Three specific genes—LCP1, RETSAT, and SFMBT2—were associated with the toxicity, particularly variants in LCP1 that showed strong statistical significance.
Article Abstract
A genetic predisposition to central nervous system (CNS) toxicity induced by antimicrobial drugs (antibiotics, antivirals, antifungals, and antiparasitic drugs) has been suspected. Whole genome sequencing of 66 cases and 833 controls was performed to investigate whether antimicrobial drug-induced CNS toxicity was associated with genetic variation. The primary objective was to test whether antimicrobial-induced CNS toxicity was associated with seventeen efflux transporters at the blood-brain barrier. In this study, variants or structural elements in efflux transporters were not significantly associated with CNS toxicity. Secondary objectives were to test whether antimicrobial-induced CNS toxicity was associated with genes over the whole genome, with HLA, or with structural genetic variation. Uncommon variants in and close to three genes were significantly associated with CNS toxicity according to a sequence kernel association test combined with an optimal unified test (SKAT-O). These genes were LCP1 (q = 0.013), RETSAT (q = 0.013) and SFMBT2 (q = 0.035). Two variants were driving the LCP1 association: rs6561297 (p = 1.15x10-6, OR: 4.60 [95% CI: 2.51-8.46]) and the regulatory variant rs10492451 (p = 1.15x10-6, OR: 4.60 [95% CI: 2.51-8.46]). No common genetic variant, HLA-type or structural variation was associated with CNS toxicity. In conclusion, CNS toxicity due to antimicrobial drugs was associated with uncommon variants in LCP1, RETSAT and SFMBT2.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903854 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0299075 | PLOS |
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