Evidence map›Paper›PMID 39208774›Full record

ArticleInternational archives of allergy and immunology2025

Functional Polymorphisms Regulate FOXO1 Transcript Expression and Contribute to the Risk and Symptom Severity of HDM-Induced Allergic Rhinitis.

Yang Yie Sio, Kefan Du, Terence Yin Weng Lam, Yee-How Say, Kavita Reginald, Fook Tim Chew

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Article in International archives of allergy and immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

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4citing papers in PubMed
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3 · Its place in the literature

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4 citing papers in PubMed.

  1. Article
  2. A Functional Variant ofJournal of asthma and allergy · 2026
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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Yang Yie SioDepartment of Biological Sciences, National University of Singapore, Singapore, Singapore, dbssioy@nus.edu.sg.
Kefan DuDepartment of Biological Sciences, National University of Singapore, Singapore, Singapore.
Terence Yin Weng LamDepartment of Biological Sciences, National University of Singapore, Singapore, Singapore.
Yee-How SayDepartment of Biological Sciences, National University of Singapore, Singapore, Singapore.
Kavita ReginaldDepartment of Biological Sciences, School of Medical and Life Sciences, Sunway University, Subang Jaya, Malaysia.
Fook Tim ChewDepartment of Biological Sciences, National University of Singapore, Singapore, Singapore.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionFOXO1 plays an important role in regulating immune processes that contribute to allergic inflammation; however, genetic variants influencing FOXO1 expression in AR pathogenesis remains unclear. This study aimed to investigate the functional effect of FOXO1 single nucleotide polymorphisms (SNPs) on AR development by performing genetic association and functional analysis studies.

methodsThis study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES). We assessed the associations of FOXO1 transcript expression levels in peripheral blood mononuclear cells (PBMC) with AR phenotype, total nasal symptom score (TNSS), and SNP genotype in a sub-cohort of n = 658 individuals from the SMCSGES population. Associations of FOXO1 SNPs with AR were assessed in a cohort of n = 5,072 individuals from the SMCSGES population. In vitro promoter luciferase assay was used to evaluate the effect of AR-associated SNPs on FOXO1 promoter activity.

resultsFOXO1 transcript expression in PBMC was significantly associated with the risk of AR (p < 0.05) and TNSS among AR patients (p < 0.0001). We identified a significant association between tag-SNPs rs9549246 and FOXO1 transcript expression in PBMC from the SMCSGES sub-cohort and the multiethnic eQTLGen consortium (false discovery rate-adjusted p < 0.05). The minor allele "A" of tag-SNP rs9549246 was significantly associated with a higher risk of AR (p = 0.04422, odds ratio = 1.21, 95% confidence interval = 1.01-1.45) in the SMCSGES genotyping cohort (n = 5,072). In vitro luciferase assay showed the minor allele "A" of rs35594717 (tagged by rs9549246) was significantly associated with a higher FOXO1 promoter activity (p < 0.05).

conclusionFOXO1 transcript expression in PBMC has a strong association with the risk and symptom severity of AR. Genetic variants tagged by rs9549246 were shown to affect the expression of FOXO1 and contribute to the development of AR in the SMCSGES population.

Indexed as

Forkhead Box Protein O1Gene Expression RegulationPolymorphism, Single NucleotideRhinitis, AllergicAdultCross-Sectional StudiesFemaleGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHumansLeukocytes, MononuclearMaleMiddle AgedPromoter Regions, GeneticSeverity of Illness IndexForkhead Box Protein O1FOXO1 protein, humanAllergic rhinitisAllergyFOXO1Peripheral blood mononuclear cellSingle nucleotide polymorphism

Identifiers

PMID39208774
PMCPMC11731838

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