PMID- 38137494 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231225 IS - 2227-9059 (Print) IS - 2227-9059 (Electronic) IS - 2227-9059 (Linking) VI - 11 IP - 12 DP - 2023 Dec 11 TI - Genetic Susceptibility of HLA Alleles to Non-Steroidal Anti-Inflammatory Drug Hypersensitivity in the Taiwanese Population. LID - 10.3390/biomedicines11123273 [doi] LID - 3273 AB - BACKGROUND: Human leukocyte antigen (HLA) genes are important in many immune processes and contribute to many adverse drug reactions. Whether genetic variations in the HLA region are associated with non-steroid anti-inflammatory drug (NSAID) hypersensitivity remains uncertain. Therefore, the aim of our study was to identify HLA genetic variations in patients with NSAID hypersensitivity in the Taiwanese population. METHODS: This hospital-based, retrospective case-control study enrolled 37,156 participants with NSAID exposure from the Taiwan Precision Medicine Initiative (TPMI), who were all genotyped and imputed to fine map HLA typing. Our study assigned 1217 cases to the NSAID allergy group and 12,170 controls to a matched group. Logistic regression analyses were utilized to explore associations between HLA alleles and NSAID hypersensitivity. RESULTS: Overall, 13,387 patients were genotyped for eight major HLA alleles. Allele frequencies were different between the two groups. In the NSAID allergy group, the genotype frequencies of HLA-A*02:01, HLA-A*34:01, and HLA-DQA1*06:01 were found to be markedly elevated compared to the control group, a significance that persisted even after applying the Bonferroni correction. Furthermore, the risk of NSAID allergy demonstrated a significant association with HLA-A*02:01 (OR = 1.29, p < 0.001) and HLA-A*34:01 (OR = 9.90, p = 0.001), in comparison to their respective counterparts. Notably, the genotype frequency of HLA-B*46:01 exhibited a significant increase in the severe allergy group when compared with the mild allergy group. CONCLUSIONS: We identified HLA genotypes linked to the onset and severity of NSAID hypersensitivity. Our findings establish a basis for precision prescription in future clinical applications. FAU - Chang, Szu-Ling AU - Chang SL AUID- ORCID: 0000-0002-5180-7803 AD - Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407219, Taiwan. AD - Department of Postbaccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402202, Taiwan. AD - Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan. FAU - Lai, Chih-Hung AU - Lai CH AUID- ORCID: 0000-0003-1409-4979 AD - Department of Postbaccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402202, Taiwan. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan. AD - Department of Medicine and Cardiovascular Center, Taichung Veterans General Hospital, Taichung 407219, Taiwan. FAU - Lin, Guan-Cheng AU - Lin GC AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung 407219, Taiwan. FAU - Chen, Yi-Ming AU - Chen YM AD - Department of Postbaccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402202, Taiwan. AD - School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan. AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung 407219, Taiwan. AD - Division of Allergy, Immunology and Rheumatology, Department of Medical Research, Taichung Veterans General Hospital, Taichung 407219, Taiwan. AD - Institute of Biomedical Science and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402202, Taiwan. FAU - Lee, Mei-Hsuan AU - Lee MH AUID- ORCID: 0000-0002-0222-2251 AD - Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan. FAU - Hsu, Han-Shui AU - Hsu HS AD - Institute of Emergency and Critical Care Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan. AD - Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 112201, Taiwan. FAU - Chen, I-Chieh AU - Chen IC AUID- ORCID: 0000-0002-8345-5304 AD - Department of Medical Research, Taichung Veterans General Hospital, Taichung 407219, Taiwan. LA - eng GR - NSTC -110-2634-F-A49-005, NSTC-111-2218-E-039-001, and NSTC-111-2314-B-075A-003-MY3/Ministry of Science and Technology, Taiwan/ GR - TCVGH-1127304B, TCVGH-1127301C, TCVGH-1127302D, and TCVGH-YM1120110/Taichung Veterans General Hospital/ PT - Journal Article DEP - 20231211 PL - Switzerland TA - Biomedicines JT - Biomedicines JID - 101691304 PMC - PMC10741656 OTO - NOTNLM OT - HLA alleles OT - NSAID hypersensitivity OT - drug allergy OT - genotypes OT - imputation COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest. The authors have no relevant financial or non-financial interests to disclose. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. EDAT- 2023/12/23 12:44 MHDA- 2023/12/23 12:45 PMCR- 2023/12/11 CRDT- 2023/12/23 01:10 PHST- 2023/10/25 00:00 [received] PHST- 2023/12/06 00:00 [revised] PHST- 2023/12/08 00:00 [accepted] PHST- 2023/12/23 12:45 [medline] PHST- 2023/12/23 12:44 [pubmed] PHST- 2023/12/23 01:10 [entrez] PHST- 2023/12/11 00:00 [pmc-release] AID - biomedicines11123273 [pii] AID - biomedicines-11-03273 [pii] AID - 10.3390/biomedicines11123273 [doi] PST - epublish SO - Biomedicines. 2023 Dec 11;11(12):3273. doi: 10.3390/biomedicines11123273.