دورية أكاديمية
Four-digit HLA type association test.
| العنوان: | Four-digit HLA type association test. |
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| المؤلفون: | Joel Ås, Ilma Bertulyte, Nina Norgren, Anna Johansson, Niclas Eriksson, Henrik Green, Mia Wadelius, Pär Hallberg |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Biochemistry, Genetics, Neuroscience, Pharmacology, Cancer, Infectious Diseases, Virology, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, regulatory variant rs10492451, optimal unified test, central nervous system, 51 – 8, test whether antimicrobial, common genetic variant, whole genome sequencing, whole genome case, seventeen efflux transporters, div >< p, cns toxicity due, cns toxicity according, induced cns toxicity, structural genetic variation, 013 ), retsat, whole genome, toxicity induced, efflux transporters, cns toxicity |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://figshare.com/articles/journal_contribution/Four-digit_HLA_type_association_test_/25317510Test |
| DOI: | 10.1371/journal.pone.0299075.s006 |
| الإتاحة: | https://doi.org/10.1371/journal.pone.0299075.s006Test https://figshare.com/articles/journal_contribution/Four-digit_HLA_type_association_test_/25317510Test |
| حقوق: | CC BY 4.0 |
| رقم الانضمام: | edsbas.E30E1E4D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1371/journal.pone.0299075.s006 |
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