Genome-Wide Risk Assessment and Clinical Prediction of Iodinated Contrast Media-Induced Anaphylaxis.
12 affiliations
- 1Department of Pulmonology and Allergy, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, Korea.
- 2Allergy and Clinical Immunology Research Center, Hallym University College of Medicine, Chuncheon, Korea.
- 3JS Link, Inc., Seoul, Korea.
- 4Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea.
- 5Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
- 6Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
- 7Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
- 8Institute of Allergy and Clinical Immunology, Medical Research Center, Seoul National University, Seoul, Korea.
- 9AgingLab Inc., Ulsan, Korea.
- 10Korean Genomics Center, Ulsan National Institute of Science and Technology, Ulsan, Korea.
- 11Institute of Allergy and Clinical Immunology, Medical Research Center, Seoul National University, Seoul, Korea. [email protected].
- 12Institute of Allergy and Clinical Immunology, Medical Research Center, Seoul National University, Seoul, Korea. [email protected].
Abstract
Purpose
Iodinated contrast media (ICM) are widely used in diagnostic imaging, but may trigger immediate hypersensitivity reactions, including anaphylaxis. Although human leukocyte antigen (HLA) associations have been proposed, genome-wide evidence remains limited. To identify genetic risk variants associated with ICM-induced anaphylaxis and evaluate their clinical utility.Methods
We conducted a genome-wide association study (GWAS) in 91 Korean patients with confirmed ICM-induced anaphylaxis (discovery, n = 67; replication, n = 24) and 1,565 controls. Genotyping used a Korean-specific single nucleotide polymorphism (SNP) array. Significant variants were replicated. HLA alleles were imputed in the combined dataset. Linkage disequilibrium (LD) among significant loci was analyzed. Cumulative genetic burden was assessed by summing risk alleles per individual. A Least Absolute Shrinkage and Selection Operator-based prediction model incorporated genetic and clinical variables.Results
Nineteen SNPs reached genome-wide significance and were replicated, including rs2229629 in HK2 (odds ratio, 5.02; P = 9.6 × 10⁻²³), suggesting altered glycolysis. Additional variants were found near GABBR1, ZNF391, ATAT1, and HLA genes. Imputed HLA-DRB1*15:02 was significantly enriched in patients (41.8% vs. 5.9%, P = 5.21 × 10⁻¹⁷). LD analysis showed haplotypic clustering within HLA and non-HLA loci. A gene dosage effect was observed. The combined genetic-clinical model showed the highest predictive performance (area under the curve [AUC] = 0.888), exceeding genetic (AUC = 0.800) and clinical (AUC = 0.835) models.Conclusions
This first GWAS of ICM-induced anaphylaxis identifies susceptibility loci across metabolic, immune, and neuroimmune pathways. HK2 was most strongly associated, and HLA-DRB1*15:02 was robustly replicated.
Related
- Evaluation of a personalized total iodine dose (TID) combined with fixed injection duration (FID) protocol using high-concentration (400 mgI/mL) iodinated contrast medium in CT portal venography: a randomized trial
- T cell–mediated reactions to iodinated contrast media: Evaluation by skin and lymphocyte activation tests
- Prospective evaluation of risk factors for acute adverse reactions to iodinated contrast media in contrast-enhanced CT.
- A Clinical Perspective on Multidimensional Assessment of Clinical High-Risk States for Psychosis Beyond Transition Prediction
- Contrast-enhanced ultrasound in assessment of testicular injury based on different degrees of testicular torsion in rabbits
BibTeX
@article{chung2026genomewide,
title = {{Genome-Wide Risk Assessment and Clinical Prediction of Iodinated Contrast Media-Induced Anaphylaxis.}},
author = {Soo Jie Chung and Eunsoon Shin and Yong-Seok Kim and So-Hee Lee and Sun-Sin Kim and Sun Young Paik and Heung-Woo Park and Sae-Hoon Kim and Sungwon Jeon and Jong Bhak and Hye-Ryun Kang and Yoon-Seok Chang},
journal = {Allergy, asthma \& immunology research},
year = {2026},
month = sep,
doi = {10.4168/aair.2026.18.5.776},
url = {https://europepmc.org/article/MED/42845231},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Genome-Wide Risk Assessment and Clinical Prediction of Iodinated Contrast Media-Induced Anaphylaxis.
AU - Soo Jie Chung
AU - Eunsoon Shin
AU - Yong-Seok Kim
AU - So-Hee Lee
AU - Sun-Sin Kim
AU - Sun Young Paik
AU - Heung-Woo Park
AU - Sae-Hoon Kim
AU - Sungwon Jeon
AU - Jong Bhak
AU - Hye-Ryun Kang
AU - Yoon-Seok Chang
PY - 2026
DA - 2026/09/01
JO - Allergy, asthma & immunology research
DO - 10.4168/aair.2026.18.5.776
UR - https://europepmc.org/article/MED/42845231
AB - Purpose Iodinated contrast media (ICM) are widely used in diagnostic imaging, but may trigger immediate hypersensitivity reactions, including anaphylaxis. Although human leukocyte antigen (HLA) associations have been proposed, genome-wide evidence remains limited. To identify genetic risk variants associated with ICM-induced anaphylaxis and evaluate their clinical utility.Methods We conducted a genome-wide association study (GWAS) in 91 Korean patients with confirmed ICM-induced anaphylaxis (discovery, n = 67; replication, n = 24) and 1,565 controls. Genotyping used a Korean-specific single nucleotide polymorphism (SNP) array. Significant variants were replicated. HLA alleles were imputed in the combined dataset. Linkage disequilibrium (LD) among significant loci was analyzed. Cumulative genetic burden was assessed by summing risk alleles per individual. A Least Absolute Shrinkage and Selection Operator-based prediction model incorporated genetic and clinical variables.Results Nineteen SNPs reached genome-wide significance and were replicated, including rs2229629 in HK2 (odds ratio, 5.02; P = 9.6 × 10⁻²³), suggesting altered glycolysis. Additional variants were found near GABBR1, ZNF391, ATAT1, and HLA genes. Imputed HLA-DRB1*15:02 was significantly enriched in patients (41.8% vs. 5.9%, P = 5.21 × 10⁻¹⁷). LD analysis showed haplotypic clustering within HLA and non-HLA loci. A gene dosage effect was observed. The combined genetic-clinical model showed the highest predictive performance (area under the curve [AUC] = 0.888), exceeding genetic (AUC = 0.800) and clinical (AUC = 0.835) models.Conclusions This first GWAS of ICM-induced anaphylaxis identifies susceptibility loci across metabolic, immune, and neuroimmune pathways. HK2 was most strongly associated, and HLA-DRB1*15:02 was robustly replicated.
SN - 2092-7355
SN - 2092-7363
ER -