Genetic variations associated with immediate hypersensitivity reactions to iodinated contrast media: A whole exome sequencing study

by Noeul Kang, Hoshik Kwon, Myung-Eui Seo, Byung-Joo Min, Byung-Jae Lee, Ju Han Kim, Ho Yun Lee

Objective

The use of iodinated contrast media (ICM) in computed tomography (CT) has increased significantly; however, hypersensitivity reactions (HSRs) remain a concern. This study aimed to investigate genetic factors associated with ICM-induced immediate HSRs using whole exome sequencing (WES).

Materials and Methods

We conducted a case–control study including 20 patients with ICM-induced immediate HSRs and 11 controls who had received ICM at least three times without HSRs. WES was performed with DNA extracted from saliva samples. Analyses included single-nucleotide variant (SNV) association testing using the Cochran–Armitage trend test with false discovery rate (FDR) correction, gene-wise variant burden (GVB) analysis, and copy number variation (CNV) detection using complementary algorithms.

Results

A variant in FAST kinase domain 1 (FASTKD1, rs12618227) was significantly more prevalent in the control group compared with the case group (72.7% vs. 5.0%, FDR p < 0.10), suggesting a protective role. GVB analysis revealed lower scores for FASTKD1 and 2-hydroxyacyl-CoA lyase 1 (HACL1) in the control group (nominal p < 0.001). CNV analysis identified a significant Signal Regulatory Protein Beta 1 (SIRPB1) deletion in the case group (5/20, 25.0%). In contrast, CNVs in Mucin 12, cell surface associated (MUC12) were observed in both groups. Immune cell expression data showed high expression of FASTKD1, HACL1, and SIRPB1 in granulocytes, particularly basophils.

Conclusion

FASTKD1 and HACL1, which are involved in mitochondrial and metabolic regulation, and SIRPB1, which participates in innate immune signaling, were identified as candidate genes potentially associated with ICM-induced immediate HSRs. These suggest a possible contribution of both metabolic and immune regulatory pathways to genetic susceptibility and require validation in larger, independent cohorts before clinical application.