IL-1 receptor–associated kinase 3 gene (IRAK3) variants associate with asthma in a replication study in the Spanish population

Pino-Yanes, María; Sánchez‐Machín, Inmaculada; Cumplido, José; Figueroa, Javier; Torres-Galván, María José; González, Ruperto; Corrales, Almudena; Acosta-Fernández, Orlando; García-Robaina, José Carlos; Carrillo, Teresa; Sánchez-Palacios, Anselmo; Villar, Jesús; Hernández, Mariano; Flores, Carlos

doi:10.1016/j.jaci.2011.10.001

Cited by 21 publications

(23 citation statements)

References 30 publications

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“…Based on the premise that incorporating the age-at-onset in the analyses might increase the power to detect association [24], [25], we next used SA of asthma patients to estimate the age at diagnosis cutoff maximizing allele effects. For that, among the 35 SNPs that reached nominal significance, we first excluded the redundant SNPs from each gene using conditional logistic regressions for asthma or atopic asthma.…”

Section: Resultsmentioning

confidence: 99%

“…Sample details have been described elsewhere [24]. In brief, cases included 607 asthmatic patients aged >5 years and diagnosed by physicians following the Global Initiative for Asthma (GINA) guidelines for diagnosis and classification of asthma severity (http://www.ginasthma.com).…”

Section: Methodsmentioning

confidence: 99%

“…A principal component analysis (PCA) based on these genetic markers was used to derive the ancestry estimates in cases and controls as scores of the first principal component (PC1), by means of EIGENSOFT [29]. A full list of EuroAIMs used and the genotyping procedures have been detailed elsewhere [24], [28].…”

Section: Methodsmentioning

confidence: 99%

“…Among these phenotypes, the age-at-onset of asthma could differentiate asthmatic groups, so that genetic variants might inconsistently associate with childhood and later-onset disease [17], [24], [25]. Motivated by this evidence, here we aimed to assess the reliability of asthma associations for the eight most replicated non- HLA asthma candidate genes and to explore whether effects of risk alleles varied with the disease age at diagnosis.…”

Section: Introductionmentioning

confidence: 99%

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Assessing the Validity of Asthma Associations for Eight Candidate Genes and Age at Diagnosis Effects

et al. 2013

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BackgroundBefore the advent of genome-wide association studies (GWAS), ADAM33, ADRB2, CD14, MS4A2 (alias FCER1B), IL13, IL4, IL4R, and TNF constituted the most replicated non-HLA candidate genes with asthma and related traits. However, except for the IL13-IL4 region, none of these genes have been found in close proximity of genome-wide significant hits among GWAS for asthma or related traits. Here we aimed to assess the reproducibility of these asthma associations and to test if associations were more evident considering the effect of age at diagnosis.Methodology/Principal FindingsWe systematically evaluated 286 common single nucleotide polymorphisms (SNPs) of these 8 genes in a sample of 1,865 unrelated Spanish individuals (606 asthmatics and 1,259 controls). We found that variants at MS4A2, IL4R and ADAM33 genes demonstrated varying association effects with the age at diagnosis of asthma, with 10 SNPs showing study-wise significance after the multiple comparison adjustment. In addition, in silico replication with GWAS data supported the association of IL4R.Conclusions/SignificanceOur results support the important role of MS4A2, IL4R and ADAM33 genes in asthma and/or atopy susceptibility. However, additional studies in larger samples sets are needed to firmly implicate these genes in asthma susceptibility, and also to identify the causal variation underlying the associations found.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Assessing the Validity of Asthma Associations for Eight Candidate Genes and Age at Diagnosis Effects

et al. 2013

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“…7 An independent sample of 568 asthma cases and 787 controls was used for replication. For further description of the study design, see Fig E1, Online Repository text, and Table E1 in this article's Online Repository at www.jacionline.org.…”

Section: To the Editormentioning

confidence: 99%

HLA-DRB1*15:01 allele protects from asthma susceptibility

Pino-Yanes

Corrales

Acosta‐Herrera

et al. 2014

Journal of Allergy and Clinical Immunology

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Retracted: IRAK3 gene silencing prevents cardiac rupture and ventricular remodeling through negative regulation of the NF‐κB signaling pathway in a mouse model of acute myocardial infarction

Wang

et al. 2018

Journal Cellular Physiology

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Cardiac rupture and ventricular remodeling are recognized as the severe complications and major risk factors of acute myocardial infarction (AMI). This study aims to evaluate the regulatory roles of interleukin‐1 receptor‐associated kinase 3 (IRAK3) and nuclear factor‐κB (NF‐κB) signaling pathway in cardiac rupture and ventricular remodeling. Microarray analysis was performed to screen AMI‐related differentially expressed genes and IRAK3 was identified. The models of AMI were established in male C57BL/6 mice to investigate the functional role of IRAK3. Afterwards, lentivirus recombinant plasmid si‐IRAK3 was constructed for IRAK3 silencing. Next, cardiac function parameters were measured in response to IRAK3 silencing. The regulatory effects that IRAK3 had on myocardial infarct size and the content of myocardial interstitial collagen were analyzed. The regulation of IRAK3 silencing on the NF‐κB signaling pathway was further assayed. The obtained results indicated that highly expressed IRAK3 and activated NF‐κB signaling pathway were observed in myocardial tissues of mouse models of AMI, accompanied by increased expression of matrix metalloproteinase (MMP)‐2/9 and tissue inhibitor of metalloproteinase 2 (TIMP‐2). Notably, IRAK3 gene silencing inhibited the activation of NF‐κB signaling pathway. Furthermore, IRAK3 gene silencing led to the decreased thickness of infarct area and collagen content of myocardial interstitium, alleviated diastolic, and systolic dysfunctions, as well as, facilitated cardiac functions in mice with AMI, corresponding to decreased expression of MMP‐2/9 expression and increased expression of TIMP‐2. Taken together, silencing of IRAK3 inactivates the NF‐κB signaling pathway, and thereby impeding the cardiac rupture and ventricular remodeling, which eventually prevents AMI progression.

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IL-1 receptor–associated kinase 3 gene (IRAK3) variants associate with asthma in a replication study in the Spanish population

Cited by 21 publications

References 30 publications

Assessing the Validity of Asthma Associations for Eight Candidate Genes and Age at Diagnosis Effects

Assessing the Validity of Asthma Associations for Eight Candidate Genes and Age at Diagnosis Effects

HLA-DRB1*15:01 allele protects from asthma susceptibility

Retracted: IRAK3 gene silencing prevents cardiac rupture and ventricular remodeling through negative regulation of the NF‐κB signaling pathway in a mouse model of acute myocardial infarction

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