A Screening Test for HLA-B∗15:02 in a Large United States Patient Cohort Identifies Broader Risk of Carbamazepine-Induced Adverse Events
Autor: | Andria L. Del Tredici, Hua Fang, Tanya Moreno, Kulvinder Kaur, Bae J. Riley, Guangdan Zhu, Matthew Dedek, Frank G. Espin, Xiequn Xu |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Concordance Population Ethnic group 03 medical and health sciences 0302 clinical medicine Internal medicine SJS Medicine Pharmacology (medical) HLA-B∗15:02 Adverse effect education pharmacogenetics Pharmacology education.field_of_study business.industry lcsh:RM1-950 tagging SNP Minor allele frequency lcsh:Therapeutics. Pharmacology 030104 developmental biology population screening carbamazepine 030220 oncology & carcinogenesis Cohort business Risk assessment Pharmacogenetics |
Zdroj: | Frontiers in Pharmacology, Vol 10 (2019) |
ISSN: | 1663-9812 |
Popis: | Purpose: HLA-B∗15:02 is strongly associated with life-threatening severe skin hypersensitivity reactions in patients treated with carbamazepine (CBZ) and structurally related medications. FDA-approved labeling recommends HLA-B∗15:02 screening before CBZ therapy in patients of Asian ancestry. In this study, we aimed to (a) identify a direct method for screening HLA-B∗15:02, and (b) evaluate prevalence in a large cohort of United States patients. Methods: Candidate genetic markers were identified by mining public data. Association was tested in 28,897 individuals by comparing SNP results with high-resolution HLA typing. Retrospective analysis of de-identified SNP and ethnicity data from 130,460 individuals was performed to evaluate the ethnic distribution of HLA-B∗15:02 in the United States. Results: 28,897 United States individuals showed 100% concordance between HLA-B∗15:02 and the minor allele of rs144012689 (100% sensitivity/99.97% specificity). Retrospective analysis of 160 positive individuals (66 with physician-reported ethnicity) notably included 28 Asians (42%), 15 African Americans (22%), 11 Caucasians (17%), 2 Hispanics (3%), and 10 “Other” (15%). Conclusion: Screening United States patients for HLA-B∗15:02 without ethnicity-based preselection identifies more than twice the number of carriers at risk of CBZ-related adverse events than screening patients of Asian ancestry alone. Risk assessment based on ethnicity assumptions may not identify a large portion of at-risk patients in the ethnically diverse United States population. |
Databáze: | OpenAIRE |
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