Evaluation of genetic variants in ferroptosis-related genes and house dust mite-induced allergic rhinitis risk

Yi-Fan Yang; Rui Zheng; Xiang Gu; Fang Gao; Min Chen; Mu-Long Du; Zheng-Dong Zhang; Mei-Ping Lu; Lei Cheng

doi:10.1016/j.intimp.2023.109707

Evaluation of genetic variants in ferroptosis-related genes and house dust mite-induced allergic rhinitis risk

Int Immunopharmacol. 2023 Feb:115:109707. doi: 10.1016/j.intimp.2023.109707. Epub 2023 Jan 20.

Authors

Yi-Fan Yang¹, Rui Zheng², Xiang Gu¹, Fang Gao³, Min Chen⁴, Mu-Long Du⁵, Zheng-Dong Zhang², Mei-Ping Lu⁶, Lei Cheng⁷

Affiliations

¹ Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China.
² Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
³ Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China; Key Laboratory of Environmental Medicine Engineering, Ministry of Education of China, School of Public Health, Southeast University, Nanjing, China.
⁴ Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China; Department of Otorhinolaryngology-Head and Neck Surgery, Changhai Hospital, Naval Medical University, Shanghai, China.
⁵ Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China; Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
⁶ Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China. Electronic address: lumeiping@jsph.org.cn.
⁷ Department of Otorhinolaryngology & Clinical Allergy Center, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China; International Centre for Allergy Research, Nanjing Medical University, Nanjing, China. Electronic address: chenglei@jsph.org.cn.

PMID: 37724950
DOI: 10.1016/j.intimp.2023.109707

Abstract

Background: Ferroptosis-related genes disrupt iron homeostasis and enhance lipid peroxidation to initiate respiratory system diseases. However, the association between genetic variants in the ferroptosis-related genes with house dust mite (HDM)-induced allergic rhinitis (AR) susceptibility remains unclear.

Methods: A case-control study, involving 222 cases and 237 healthy controls from a Chinese population, was conducted to evaluate the relationship between single nucleotide polymorphisms (SNPs) in ferroptosis-related genes and HDM-induced AR risk. A gene-based analysis was performed by multi-marker analysis of genomic annotation (MAGMA) to identify candidate associated ferroptosis-related genes. A logistic regression model and joint analysis were used to assess the effect of SNPs on HDM-induced AR susceptibility.

Results: Two independent SNPs (rs2305128 in ENPP2 and rs1868088 in EPAS1) were significantly associated with HDM-induced AR risk (OR = 1.82, 95% CI = 1.19-2.79, P = 5.98 × 10^-3, P_FDR = 4.88 × 10^-2; OR = 2.14, 95% CI = 1.23-3.72, P = 6.95 × 10^-3, P_FDR = 4.87 × 10^-2, respectively). Moreover, combined analysis of these two SNPs revealed that an increased risk of HDM-induced AR was positively associated with an increasing number of risk genotypes (P_trend = 8.48 × 10^-5). The stratification analysis showed that the cumulative effect of two SNPs on HDM-induced AR risk was more pronounced among patients presenting more serious symptoms and harboring one or two risk genotypes.

Conclusions: These findings suggest that the genetic variants in ferroptosis-related genes ENPP2 and EPAS1 may increase HDM-induced AR risk and serve as potential predictors of HDM-induced AR susceptibility.

Keywords: Allergic rhinitis; ENPP2; EPAS1; Ferroptosis; Genetic variation; Mites.

MeSH terms

Animals
Case-Control Studies
Ferroptosis* / genetics
Genotype
Humans
Pyroglyphidae
Rhinitis, Allergic* / genetics