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Published on: December 9, 2015
Functional Impact of MRGPRX2 Single-Nucleotide Polymorphisms on Drug-Induced Cellular Responses In Vitro
Alicja Dziadowiec1, Mateusz Kwitniewski2, Hubert Rybka3,4
1Department of Clinical and Environmental Allergology, Jagiellonian University Medical College, 31-503 Krakow, Poland.
Frontiers in Bioscience (Landmark Edition)
|May 30, 2026
Summary
Investigating Mas-related G protein-coupled receptor X2 (MRGPRX2) single-nucleotide polymorphisms (SNPs) revealed that the E164R and W248L variants exhibit a loss-of-function. This suggests in silico modeling can predict MRGPRX2 variant pathogenicity in drug hypersensitivity reactions.
Area of Science:
- Pharmacology
- Genetics
- Immunology
Background:
- Mas-related G protein-coupled receptor X2 (MRGPRX2) activation by drugs like vancomycin and fluoroquinolones is implicated in drug hypersensitivity reactions (DHRs).
- Single-nucleotide polymorphisms (SNPs) in the MRGPRX2 gene may influence receptor activity and drug tolerance.
- The precise contribution of MRGPRX2 variants to DHRs requires further investigation.
Purpose of the Study:
- To assess the in vitro functional impact of selected MRGPRX2 SNPs on receptor activation by common drug ligands.
- To evaluate the predictive accuracy of in silico modeling for MRGPRX2 variant pathogenicity.
- To investigate the role of MRGPRX2 variants in modulating responses to ciprofloxacin, atracurium, and vancomycin.
Main Methods:
- Transient transfection of RBL-2H3 cells with wild-type (WT) MRGPRX2 and its variants (N62S, S313R, S325L, E164R, W248L).
- Assessment of cell-surface MRGPRX2 expression using flow cytometry.
- Measurement of intracellular calcium mobilization upon stimulation with ciprofloxacin, atracurium, vancomycin, and substance P.
Main Results:
- All MRGPRX2 variants showed comparable cell-surface expression.
- The E164R and in silico-predicted W248L variants exhibited a significant loss-of-function phenotype.
- The N62S variant displayed slightly reduced responses, while S313R and S325L variants showed responses comparable to WT MRGPRX2.
Conclusions:
- The E164R and W248L MRGPRX2 variants demonstrate loss-of-function, supporting the utility of in silico prediction for variant pathogenicity.
- N62S variant did not show enhanced responses to tested drugs, and other variants had partial concordance with prior data.
- Further studies are needed to elucidate the role of MRGPRX2 variants in DHRs, considering potential variations in experimental design.
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