Association of IL-17RB Gene Polymorphism With Asthma

Jung, Jisun; Park, Byung Lae; Cheong, Hyun Sub; Bae, Joon Seol; Kim, Jihye; Chang, Hun Soo; Rhim, Taiyoun; Park, Jong‐Sook; Jang, An‐Soo; Lee, Young Mok; Kim, Ki-Up; Uh, Soo‐Taek; Na, Ju Ock; Kim, Yong‐Hoon; Park, Choon-Sik; Shin, Hyoung Doo

doi:10.1378/chest.08-1595

Cited by 42 publications

(24 citation statements)

References 28 publications

(32 reference statements)

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“…The biological effects of IL-25 are mediated by the IL-25 receptor, composed of the subunits IL-17RA and IL-17RB, which combine to form the functional receptor for IL-25 (IL-17RA/IL-17RB) [12]. IL-25 is the high-affinity ligand for IL-17RB [24,25], and in a previous study we showed that the IL-25 receptor expression on eosinophils is higher in allergic asthmatics compared to atopic nonasthmatic and normal subjects [13]. In this study, we found that the expression of IL-17RB and the functional receptor (IL-17RA/RB) on peripheral blood eosinophils was significantly increased 24 h after the allergen challenge but not after the diluent challenge.…”

Section: Discussionmentioning

confidence: 99%

Allergen-Induced Increases in Interleukin-25 and Interleukin-25 Receptor Expression in Mature Eosinophils from Atopic Asthmatics

Tang

Smith

Salter

et al. 2016

Int Arch Allergy Immunol

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Background: Interleukin (IL)-25 plays a pivotal role in type 2 immune responses. In a baseline cross-sectional study, we previously showed that IL-25 plasma levels and IL-25 receptor (IL-25R: IL-17RA, IL-17RB, and IL-17RA/RB) expression on mature blood eosinophils are increased in atopic asthmatics compared to normal nonatopic controls. This study investigated allergen-induced changes in IL-25 and IL-25R expression in eosinophils from asthmatics. Methods: Dual responder atopic asthmatics (n = 14) were enrolled in this randomized diluent-controlled crossover allergen challenge study. Blood was collected before and 24 h after the challenge. The surface expression of IL-25R was evaluated by flow cytometry on eosinophils and Th2 memory cells. In addition, plasma levels of IL-25 were measured by ELISA, and functional responses to IL-25 including type 2 cytokine expression, degranulation, and the migrational responsiveness of eosinophils were evaluated in vitro. Results: Following the allergen but not the diluent inhalation challenge, significant increases in the expression of IL-17RB and IL-17RA/B were found on eosinophils but not on Th2 memory cells. IL-25 plasma levels and the number of eosinophils but not of Th2 memory cells expressing intracellular IL-25 increased significantly in response to the allergen but not the diluent challenge. Stimulation with physiologically relevant concentrations of IL-25 in vitro caused (i) degranulation of eosinophils (measured by eosinophil peroxidase release), (ii) enhanced intracellular expression of IL-5 and IL-13, and (iii) priming of eosinophil migration to eotaxin. IL-25 stimulated intracellular cytokine expression, and the migration of eosinophils was blocked in the presence of a neutralizing IL-25 antibody. Conclusions: Our findings suggest that the IL-25/IL-25R axis may play an important role in promoting the recruitment and proinflammatory function of eosinophils in allergic asthma.

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Section: Discussionmentioning

confidence: 99%

Allergen-Induced Increases in Interleukin-25 and Interleukin-25 Receptor Expression in Mature Eosinophils from Atopic Asthmatics

Tang

Smith

Salter

et al. 2016

Int Arch Allergy Immunol

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“…exon skipping, activation of cryptic splice sites, or alteration of the fine balance of the alternatively spliced isoforms that are produced [18]. It has also been reported that an intronic polymorphism (rs3733072) in the interleukin-17 receptor B (IL-17RB) gene is associated with the risk of asthma [19]. Thus, it is possible that rs316021 is involved in the onset of AIA by affecting the transcription process of the SLC22A2 gene.…”

Section: Discussionmentioning

confidence: 99%

Possible Association of SLC22A2 Polymorphisms with Aspirin-Intolerant Asthma

Park

Kim

Bae

et al. 2011

Int Arch Allergy Immunol

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Background: Aspirin-intolerant asthma (AIA) is a clinical syndrome characterized by acute bronchoconstriction following the ingestion of aspirin. Solute carrier family 22, member 2 (SLC22A2), also known as organic cation transporter 2 (OCT2), is predominantly expressed in the luminal membrane of airway epithelial cells and has been shown to mediate the transport of prostaglandins on the cyclooxygenase pathway which is regulated by aspirin blockage. Recently, SLC22A2-mediated uptake inhibition by several nonsteroidal anti-inflammatory drugs and decreased SLC22A2 transport activity by its genetic variants have been elucidated in asthma. Methods: To investigate the associations between AIA and genetic polymorphisms of the SLC22A2 gene, 18 variants were genotyped in 163 AIA subjects and 429 aspirin-tolerant asthma (ATA) controls. Logistic analyses were used to evaluate p values for the associations of SLC22A2 polymorphisms with AIA. Results: One common polymorphism in intron 5, i.e. rs316021, was significantly associated with susceptibility to AIA (p = 0.004, P^corr = 0.05, OR = 0.60, 95% CI = 0.43–0.85 in a codominant model). The minor allele frequency of rs316021 in the AIA group was significantly lower than that in the ATA controls. In addition, a polymorphism in intron 4 (rs3912161) and a haplotype (SLC22A2-ht3) showed significantly stronger association signals with the FEV₁ fall rate induced by aspirin provocation in AIA subjects compared with ATA controls (p = 0.004, P^corr = 0.05). Conclusion: Our findings suggest that SLC22A2 could be a susceptibility gene for aspirin intolerance in asthmatics.

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“…It was reported that introns can affect transcription efficiency [25], and another study demonstrated that variations in intronic region can lead to splicing abnormalities, which in turn may lead to human diseases [26]. It was also reported recently that a SNP located in intronic region showed an association with asthma [27]. On the other hand, in additional analysis of LD near FSIP1 in Asian populations (Chinese and Japanese) from the International HapMap Project http://hapmap.ncbi.nlm.nih.gov/, the FSIP1 gene is in LD with the thrombospondin-1 ( THBS1 or TSP-1 ) gene (Additional File 2).…”

Section: Discussionmentioning

confidence: 99%

Positive Association between Aspirin-Intolerant Asthma and Genetic Polymorphisms of FSIP1: a Case-Case Study

Kim

Park

et al. 2010

BMC Pulm Med

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BackgroundAspirin-intolerant asthma (AIA), which is caused by non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin, causes lung inflammation and reversal bronchi reduction, leading to difficulty in breathing. Aspirin is known to affect various parts inside human body, ranging from lung to spermatogenesis. FSIP1, also known as HDS10, is a recently discovered gene that encodes fibrous sheath interacting protein 1, and is regulated by amyloid beta precursor protein (APP). Recently, it has been reported that a peptide derived from APP is cleaved by α disintegrin and metalloproteinase 33 (ADAM33), which is an asthma susceptibility gene. It has also been known that the FSIP1 gene is expressed in airway epithelium.ObjectivesAim of this study is to find out whether FSIP1 polymorphisms affect the onset of AIA in Korean population, since it is known that AIA is genetically affected by various genes.MethodsWe conducted association study between 66 single nucleotide polymorphisms (SNPs) of the FSIP1 gene and AIA in total of 592 Korean subjects including 163 AIA and 429 aspirin-tolerant asthma (ATA) patients. Associations between polymorphisms of FSIP1 and AIA were analyzed with sex, smoking status, atopy, and body mass index (BMI) as covariates.ResultsInitially, 18 SNPs and 4 haplotypes showed associations with AIA. However, after correcting the data for multiple testing, only one SNP showed an association with AIA (corrected P-value = 0.03, OR = 1.63, 95% CI = 1.23-2.16), showing increased susceptibility to AIA compared with that of ATA cases. Our findings suggest that FSIP1 gene might be a susceptibility gene for aspirin intolerance in asthmatics.ConclusionAlthough our findings did not suggest that SNPs of FSIP1 had an effect on the reversibility of lung function abnormalities in AIA patients, they did show significant evidence of association between the variants in FSIP1 and AIA occurrence among asthmatics in a Korean population.

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Association of IL-17RB Gene Polymorphism With Asthma

Cited by 42 publications

References 28 publications

Allergen-Induced Increases in Interleukin-25 and Interleukin-25 Receptor Expression in Mature Eosinophils from Atopic Asthmatics

Allergen-Induced Increases in Interleukin-25 and Interleukin-25 Receptor Expression in Mature Eosinophils from Atopic Asthmatics

Possible Association of SLC22A2 Polymorphisms with Aspirin-Intolerant Asthma

Positive Association between Aspirin-Intolerant Asthma and Genetic Polymorphisms of FSIP1: a Case-Case Study

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