Sio, Yang Yie and Gan, Wei Liang and Ng, Wing Shan and Matta, Sri Anusha and Say, Yee How* and Teh, Keng Foo * and Wong, Yi Ru * and Smyrna Moti, Rawanan Shah * and Kavita, Reginald * and Chew, Fook Tim (2023) The ERBB2 Exonic Variant Pro1170Ala Modulates Mitogen-Activated Protein Kinase Signaling Cascades and Associates with Allergic Asthma. International Archives of Allergy and Immunology, 184 (10). pp. 1010-1021. ISSN 1423-0097
Full text not available from this repository.Abstract
Introduction: Previous studies have indicated the ERBB2 genetic variants in the 17q12 locus might be associated with asthma; however, the functional effects of these variants on asthma risk remain inconclusive. This study aimed to characterize the functional roles of asthma-associated ERBB2 single nucleotide polymorphisms (SNPs) in asthma pathogenesis by performing genetic association and functional analysis studies. Methods: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). Genotype-phenotype associations were assessed by performing a genotyping assay on n = 4,348 ethnic Chinese individuals from the SMCSGES cohort. The phosphorylation levels of receptors and signaling proteins in the MAPK signaling cascades, including ErbB2, EGFR, and ERK1/2, were compared across the genotypes of asthma-associated SNPs through in vitro and ex vivo approaches. Results: The ERBB2 tag-SNP rs1058808 was significantly associated with allergic asthma, with the allele "G" identified as protective against the disease (adjusted logistic p = 6.56 × 10-9, OR = 0.625, 95% CI: 0.544-0.718). The allele "G" of rs1058808 resulted in a Pro1170Ala mutation that results in lower phosphorylation levels of ErbB2 in HaCat cells (p < 0.001), whereas the overall ERBB2 mRNA expression and the phosphorylation levels of EGFR remained unaffected. In the SMCSGES cohort, individuals carrying the genotype "GG" of rs1058808 had lower phosphorylated ERK1/2 proteins in the MAPK signaling cascade. A lower phosphorylation level of ERK1/2 was also associated with reduced asthma risk. Conclusions: The present findings highlighted the involvement of a functional exonic variant of ERBB2 in asthma development via modulating the MAPK signaling cascade.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | allergic asthma; allergy; asthma genetics; ERBB2; Mitogen-activated protein kinase; |
| Subjects: | Q Science > QP Physiology Q Science > QR Microbiology R Medicine > RC Internal medicine |
| Divisions: | Others > Non Sunway Academics Sunway University > School of Medical and Life Sciences [formerly School of Healthcare and Medical Sciences until 2020] > Dept. Biological Sciences |
| Depositing User: | Ms Yong Yee Chan |
| Related URLs: | |
| Date Deposited: | 19 Jun 2024 07:26 |
| Last Modified: | 19 Jun 2024 07:26 |
| URI: | http://eprints.sunway.edu.my/id/eprint/2669 |
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