Cismaru et al. HLA and Pharmacogenetics of Metamizole-Agranulocytosis Results: Eight candidate alleles (p < 0.05) were identified in the discovery subset, of which HLA-C * 04:01 was associated with MIA in the full Swiss cohort (p < 0.01) restricted to agranulocytosis (ANC < 0.5 × 10 9 /L) cases. However, no candidate allele showed a consistent association in the Swiss, German and Spanish cohorts. Analysis of individual sequence variants in class I genes produced consistent results with HLA typing but did not reveal additional small nucleotide variants associated with MIA. Conclusion: Our results do not support an HLA-restricted T cell-mediated immune mechanism for MIA. However, we established an efficient high-resolution (threefield) eight-locus HTS HLA resequencing method to interrogate the HLA region and demonstrated the feasibility of its application to pharmacogenetic studies.
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