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Updated: Jan 6, 2026
Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Identifying Genetic Variants in Patients With Cefaclor-Induced Anaphylaxis Using Human Leukocyte Antigen Typing and
Sung-Ryeol Kim1, Da Eun Lee2, Hyun Young Jung2
1Division of Pulmonology, Allergy and Critical Care Medicine, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin-si, South Korea.
Background:
Cefaclor is a commonly prescribed β-lactam antibiotic and a known major cause of immediate-type drug hypersensitivity in Korea. However, its genetic risk factors remain poorly understood. We aimed to identify genetic variants associated with cefaclor-induced anaphylaxis and evaluate their potential clinical implications.
Methods:
Whole-exome sequencing and HLA genotyping were performed in 33 patients with cefaclor-induced anaphylaxis and 41 drug-tolerant controls. Associations were assessed using logistic regression. Selected variants were validated in an independent Korean population. Gene set enrichment analysis (GSEA) was performed using association statistics from all variants to investigate relevant biological pathways.
Results:
A rare missense variant, rs765144578 in TPSAB1 was strongly associated with anaphylaxis and remained significant in the validation control group. It was found in 90.91% of patients with hypotension, suggesting a link to reaction severity. Rs192498095 in HLA-DRB5 showed a significant association in the discovery cohort. However, it was not detected in the replication set, likely due to its rarity and polymorphic nature. Co-occurrence of rs765144578 in TPSAB1 and rs192498095 in HLA-DRB5 markedly increased risk. GSEA revealed significant enrichment of the TNF-α signaling via NF-κB pathway, reflecting pathway-level immune activation.
Conclusion:
Genetic variants in TPSAB1 and HLA-DRB5 may contribute to the risk of cefaclor-induced anaphylaxis, and TPSAB1 may also be associated with severity. These findings may support the development of future screening strategies or individualized risk prediction models in β-lactam allergy.
