Abstract
Introduction: NLRP3 is involved in Th2 cell differentiation and the pathogenesis of allergic rhinitis. The purpose of this study was to explore the significance of NLRP3 polymorphisms in the susceptibility to allergic rhinitis. Methods: From March 2023 to November 2024, children with allergic rhinitis (n = 200) and healthy children (n = 200) were collected. Tag single nucleotide polymorphisms (SNPs) were screened by Haploview 4.2 software. Multiplex PCR and sequencing were used to analyze genotypes of SNPs. HaploReg (version 4.2) was used to predict the impact of SNPs on regulatory motifs. Results: Five tag SNPs were obtained, which were rs10925025, rs72553860, rs870381, rs10925018, and rs10802502. The relationship between genotypes of different polymorphic loci and polymorphism was analyzed. There were significant differences in the distribution frequency of the CC, CT, and TT genotypes of NLRP3 rs10925018 between allergic rhinitis and healthy children. The rs10925018 T allele was associated with an increased risk of allergic rhinitis (OR = 1.349, 95% CI: 1.012–1.798, p = 0.041). The genotype frequency distribution of NLRP3 rs10925018 was statistically different in the serum IgE levels subgroup (p = 0.036). The rs10925018 T allele was associated with an increased risk of serum IgE levels (OR = 1.660, 95% CI: 1.105–2.493, p = 0.014). Through HaploReg prediction, the rs10925018 polymorphism may affect regulatory motifs, thereby affecting the binding of YY1 and NLRP3. Conclusions:NLRP3 rs10925018 polymorphism may be associated with susceptibility to allergic rhinitis and high IgE phenotype in children with allergic rhinitis.
Journal Section:
Clinical Allergy
References
1.
Bousquet
J
, Anto
JM
, Bachert
C
, Baiardini
I
, Bosnic-Anticevich
S
, Walter Canonica
G
, et al. Allergic rhinitis
. Nat Rev Dis Primers
. 2020
;6
(1
):95
. 2.
Weaver-Agostoni
J
, Kosak
Z
, Bartlett
S
. Allergic rhinitis: rapid evidence review
. Am Fam Physician
. 2023
;107
(5
):466
–73
.3.
Schuler Iv
CF
, Montejo
JM
. Allergic rhinitis in children and adolescents
. Pediatr Clin North Am
. 2019
;66
(5
):981
–93
. 4.
Graif
Y
, Garty
B
, Livne
I
, Green
MS
, Shohat
T
. Prevalence and risk factors for allergic rhinitis and atopic eczema among schoolchildren in Israel: results from a national study
. Ann Allergy Asthma Immunol
. 2004
;92
(2
):245
–9
. 5.
Rutkowski
K
, Sowa
P
, Rutkowska-Talipska
J
, Sulkowski
S
, Rutkowski
R
. Allergic diseases: the price of civilisational progress
. Postepy Dermatol Alergol
. 2014
;31
(2
):77
–83
. 6.
Choi
BY
, Han
M
, Kwak
JW
, Kim
TH
. Genetics and epigenetics in allergic rhinitis
. Genes
. 2021
;12
(12
):2004
. 7.
Kef
K
, Güven
S
. The prevalence of allergic rhinitis and associated risk factors among university students in anatolia
. J Asthma Allergy
. 2020
;13
:589
–97
. 8.
Hu
X
, Liu
S
, Jing
Z
, He
Y
, Qin
G
, Jiang
L
. Immunomodulation in allergic rhinitis: insights from th2 cells and NLRP3/IL‐18 pathway
. Cell Biochem Funct
. 2024
;42
(3
):e3997
. 9.
D'Elia
C
, Gozal
D
, Bruni
O
, Goudouris
E
, Meira E Cruz
M
, Cruz
M
. Allergic rhinitis and sleep disorders in children – coexistence and reciprocal interactions
. J Pediatr
. 2022
;98
(5
):444
–54
. 10.
Potaczek
DP
, Kabesch
M
. Current concepts of IgE regulation and impact of genetic determinants
. Clin Exp Allergy
. 2012
;42
(6
):852
–71
. 11.
Hellman
L
. Regulation of IgE homeostasis, and the identification of potential targets for therapeutic intervention
. Biomed Pharmacother
. 2007
;61
(1
):34
–49
. 12.
Motta
V
, Soares
F
, Sun
T
, Philpott
DJ
. NOD-like receptors: versatile cytosolic sentinels
. Physiol Rev
. 2015
;95
(1
):149
–78
. 13.
Alhazmi
A
. NOD-like receptor(s) and host immune responses with pseudomonas aeruginosa infection
. Inflamm Res
. 2018
;67
(6
):479
–93
. 14.
Kim
YK
, Shin
J
, Nahm
MH
. NOD-like receptors in infection, immunity, and diseases
. Yonsei Med J
. 2016
;57
(1
):5
–14
. 15.
Lee
M
, Ko
Y
, Jang
S
, Gil
CH
, Eun
KM
, Zhang
Y
, et al. NLRP3 inhibition attenuates the allergic rhinitis symptoms in a mouse model
. Asian Pac J Allergy Immunol
. 2024
. 16.
Zhou
H
, Zhang
W
, Qin
D
, Liu
P
, Fan
W
, Lv
H
, et al. Activation of NLRP3 inflammasome contributes to the inflammatory response to allergic rhinitis via macrophage pyroptosis
. Int Immunopharmacol
. 2022
;110
:109012
. 17.
Phan
L
, Zhang
H
, Wang
Q
, Villamarin
R
, Hefferon
T
, Ramanathan
A
, et al. The evolution of dbSNP: 25 years of impact in genomic research
. Nucleic Acids Res
. 2025
;53
(D1
):D925
–31
. 18.
Sljivancanin Jakovljevic
T
, Martic
J
, Jacimovic
J
, Nikolic
N
, Milasin
J
, Mitrović
TL
. Association between innate immunity gene polymorphisms and neonatal sepsis development: a systematic review and meta-analysis
. World J Pediatr
. 2022
;18
(10
):654
–70
. 19.
Dahmer
MK
, Cornell
T
, Quasney
MW
. Genetic and epigenetic factors in the regulation of the immune response
. Curr Opin Pediatr
. 2016
;28
(3
):281
–6
. 20.
Cheng
N
, Wang
Y
, Gu
Z
. Understanding the role of NLRP3-mediated pyroptosis in allergic rhinitis: a review
. Biomed Pharmacother
. 2023
;165
:115203
. 21.
Wo
B
, Du
C
, Yang
Y
, Qi
H
, Liang
Z
, He
C
, et al. Human placental extract regulates polarization of macrophages via IRGM/NLRP3 in allergic rhinitis
. Biomed Pharmacother
. 2023
;160
:114363
. 22.
Zhang
X
, Sun
N
, Huang
Y
, Duan
Y
, Zhang
R
. Role of NLRP3 in the exacerbation of ozone-induced allergic rhinitis
. Ecotoxicol Environ Saf
. 2023
;265
:115506
. 23.
Li
Y
, Li
R
, Li
Y
, Li
G
, Zhao
Y
, Mou
H
, et al. Transcription factor TCF3 promotes macrophage-mediated inflammation and MMP secretion in abdominal aortic aneurysm by regulating mir-143-5p /CCL20
. J Cardiovasc Pharmacol
. 2023
;82
(6
):458
–69
. 24.
Lee
WH
, Hong
KJ
, Li
HB
, Lee
GR
. Transcription factor id1 plays an essential role in th9 cell differentiation by inhibiting tcf3 and tcf4
. Adv Sci
. 2023
;10
(35
):e2305527
. 25.
Zhang
F
, Fuss
IJ
, Yang
Z
, Strober
W
. Transcription of RORγt in developing th17 cells is regulated by e-proteins
. Mucosal Immunol
. 2014
;7
(3
):521
–32
. 26.
Wöhner
M
, Tagoh
H
, Bilic
I
, Jaritz
M
, Poliakova
DK
, Fischer
M
, et al. Molecular functions of the transcription factors e2a and e2-2 in controlling germinal center b cell and plasma cell development
. J Exp Med
. 2016
;213
(7
):1201
–21
. 27.
Ben Khalaf
N
, Al-Mashoor
W
, Saeed
A
, Al-Mehatab
D
, Taha
S
, Bakhiet
M
, et al. The mouse intron-nested gene, israa, is expressed in the lymphoid organs and involved in t-cell activation and signaling
. Mol Immunol
. 2019
;111
:209
–19
. 28.
Choi
H
, Geng
Y
, Cho
H
, Li
S
, Giri
PK
, Felio
K
, et al. Differential requirements for the ets transcription factor elf-1 in the development of NKT cells and NK cells
. Blood
. 2011
;117
(6
):1880
–7
. 29.
Seifert
LL
, Si
C
, Saha
D
, Sadic
M
, de Vries
M
, Ballentine
S
, et al. The ETS transcription factor ELF1 regulates a broadly antiviral program distinct from the type i interferon response
. PLoS Pathog
. 2019
;15
(11
):e1007634
. 30.
Yoo
KH
, Kim
YN
, Lee
MJ
, Seong
JK
, Park
JH
. Identification of apolipoproteina1 reduction in the polycystic kidney by proteomics analysis of the mxi1‐deficient mouse
. Proteomics
. 2009
;9
(15
):3824
–32
. 31.
Dhanasekaran
R
, Deutzmann
A
, Mahauad-Fernandez
WD
, Hansen
AS
, Gouw
AM
, Felsher
DW
. The MYC oncogene: the grand orchestrator of cancer growth and immune evasion
. Nat Rev Clin Oncol
. 2022
;19
(1
):23
–36
. 32.
Ning
L
, Wei
W
, Wenyang
J
, Rui
X
, Qing
G
. Cytosolic DNA‐STING‐NLRP3 axis is involved in murine acute lung injury induced by lipopolysaccharide
. Clin Transl Med
. 2020
;10
(7
):e228
. 33.
Chandran
R
, Knobloch
TJ
, Anghelina
M
, Agarwal
S
. Biomechanical signals upregulate myogenic gene induction in the presence or absence of inflammation
. Am J Physiol Cell Physiol
. 2007
;293
(1
):C267
–76
. 34.
Bergsland
M
, Covacu
R
, Perez Estrada
C
, Svensson
M
, Brundin
L
. Nitric oxide-induced neuronal to glial lineage fate-change depends on NRSF/REST function in neural progenitor cells
. Stem Cell
. 2014
;32
(9
):2539
–49
. 35.
Zhang
H
, Yu
S
, Xia
L
, Peng
X
, Wang
S
, Yao
B
. NLRP3 inflammasome activation enhances ADK expression to accelerate epilepsy in mice
. Neurochem Res
. 2022
;47
(3
):713
–22
. 36.
Buffolo
F
, Petrosino
V
, Albini
M
, Moschetta
M
, Carlini
F
, Floss
T
, et al. Neuroinflammation induces synaptic scaling through IL-1β-mediated activation of the transcriptional repressor REST/NRSF
. Cell Death Dis
. 2021
;12
(2
):180
. 37.
Noyes
HA
, Alimohammadian
MH
, Agaba
M
, Brass
A
, Fuchs
H
, Gailus-Durner
V
, et al. Mechanisms controlling anaemia in trypanosoma congolense infected mice
. PLoS One
. 2009
;4
(4
):e5170
. 38.
Xu
J
, Fu
L
, Deng
J
, Zhang
J
, Zou
Y
, Liao
L
, et al. Mir-301a deficiency attenuates the macrophage migration and phagocytosis through YY1/CXCR4 pathway
. Cells
. 2022
;11
(24
):3952
. 39.
Fu
X
, Xiao
P
, Luo
X
, Guo
N
. Transcription factor YY1 accelerates hepatic fibrosis development by activating NLRP3 inflammasome-mediated pyroptosis
. Histol Histopathol
. 2024
;39
(8
):1079
–87
. 40.
Liu
H
, Schmidt-Supprian
M
, Shi
Y
, Hobeika
E
, Barteneva
N
, Jumaa
H
, et al. Yin yang 1 is a critical regulator of b-cell development
. Genes Dev
. 2007
;21
(10
):1179
–89
. 41.
Arenzana
TL
, Smith-Raska
MR
, Reizis
B
. Transcription factor zfx controls BCR-induced proliferation and survival of b lymphocytes
. Blood
. 2009
;113
(23
):5857
–67
. 42.
Smith-Raska
MR
, Arenzana
TL
, D Cruz
LM
, Khodadadi-Jamayran
A
, Tsirigos
A
, Goldrath
AW
, et al. The transcription factor zfx regulates peripheral t cell self-renewal and proliferation
. Front Immunol
. 2018
;9
:1482
. 43.
Zhang
Y
, Yang
W
, Li
W
, Zhao
Y
. NLRP3 inflammasome: checkpoint connecting innate and adaptive immunity in autoimmune diseases
. Front Immunol
. 2021
;12
:732933
. 44.
Li
R
, Wang
J
, Li
R
, Zhu
F
, Xu
W
, Zha
G
, et al. ATP/p2x7-NLRP3 axis of dendritic cells participates in the regulation of airway inflammation and hyper-responsiveness in asthma by mediating HMGB1 expression and secretion
. Exp Cell Res
. 2018
;366
(1
):1
–15
. 45.
Ma
M
, Li
G
, Qi
M
, Jiang
W
, Zhou
R
. Inhibition of the inflammasome activity of NLRP3 attenuates HDM-induced allergic asthma
. Front Immunol
. 2021
;12
:718779
. 46.
Martinon
F
, Burns
K
, Tschopp
J
. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta
. Mol Cell
. 2002
;10
(2
):417
–26
. 47.
Liston
A
, Masters
SL
. Homeostasis-altering molecular processes as mechanisms of inflammasome activation
. Nat Rev Immunol
. 2017
;17
(3
):208
–14
. 48.
Broz
P
, Dixit
VM
. Inflammasomes: mechanism of assembly, regulation and signalling
. Nat Rev Immunol
. 2016
;16
(7
):407
–20
. 49.
Besnard
AG
, Guillou
N
, Tschopp
J
, Erard
F
, Couillin
I
, Iwakura
Y
, et al. NLRP3 inflammasome is required in murine asthma in the absence of aluminum adjuvant
. Allergy
. 2011
;66
(8
):1047
–57
. 50.
Kim
RY
, Pinkerton
JW
, Essilfie
AT
, Robertson
AAB
, Baines
KJ
, Brown
AC
, et al. Role for NLRP3 inflammasome–mediated, IL-1β–dependent responses in severe, steroid-resistant asthma
. Am J Respir Crit Care Med
. 2017
;196
(3
):283
–97
. 51.
Zhou
H
, Wang
L
, Lv
W
, Yu
H
. The NLRP3 inflammasome in allergic diseases: mechanisms and therapeutic implications
. Clin Exp Med
. 2024
;24
(1
):231
. 52.
Ward
LD
, Kellis
M
. HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease
. Nucleic Acids Res
. 2016
;44
(D1
):D877
–81
. 53.
Qin
W
, Weng
J
. Hepatocyte NLRP3 interacts with PKCε to drive hepatic insulin resistance and steatosis
. Sci Bull
. 2023
;68
(13
):1413
–29
. 54.
Potaczek
DP
, Maeda
K
, Wang
Q
, Nakano
N
, Kanada
S
, Stepien
E
, et al. FcepsilonRIalpha gene -18483A>C polymorphism affects transcriptional activity through YY1 binding
. Immunogenetics
. 2009
;61
(9
):649
–55
. 55.
Poole
JA
, Rosenwasser
LJ
. The role of immunoglobulin e and immune inflammation: implications in allergic rhinitis
. Curr Allergy Asthma Rep
. 2005
;5
(3
):252
–8
. 56.
Zhuang
J
, Cui
H
, Zhuang
L
, Zhai
Z
, Yang
F
, Luo
G
, et al. Bronchial epithelial pyroptosis promotes airway inflammation in a murine model of toluene diisocyanate-induced asthma
. Biomed Pharmacother
. 2020
;125
:109925
. 57.
Sharma
V
, Michel
S
, Gaertner
V
, Franke
A
, Vogelberg
C
, von Berg
A
, et al. Fine-mapping of IgE-associated loci 1q23, 5q31, and 12q13 using 1000 genomes project data
. Allergy
. 2014
;69
(8
):1077
–84
. © 2025 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2025
You do not currently have access to this content.
