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Genetic polymorphisms and risk of recurrent wheezing in pediatric age.

ABSTRACT: Wheezing during early life is a very common disorder, but the reasons underlying the different wheezing phenotypes are still unclear. The aims of this study were to analyse the potential correlations between the risk of developing recurrent wheezing and the presence of specific polymorphisms of some genes regulating immune system function, and to study the relative importance of the associations of different viruses and genetic polymorphisms in causing recurrent episodes.The study involved 119 otherwise healthy infants admitted to hospital for a first episode of wheezing (74 of whom subsequently experienced recurrent episodes) and 119 age- and sex-matched subjects without any history of respiratory problem randomly selected from those attending our outpatient clinic during the study period. All of the study subjects were followed up for two years, and 47 single nucleotide polymorphisms (SNPs) in 33 candidate genes were genotyped on whole blood using an ABI PRISM 7900 HT Fast Real-time instrument.IL8-rs4073AT, VEGFA-rs833058CT, MBL2-rs1800450CT and IKBKB-rs3747811AT were associated with a significantly increased risk of developing wheezing (p?=?0.02, p?=?0.03, p?=?0.05 and p?=?0.0018), whereas CTLA4-rs3087243AG and NFKBIB-rs3136641TT were associated with a significantly reduced risk (p?=?0.05 and p?=?0.04). IL8-rs4073AT, VEGFA-rs2146323AA and NFKBIA-rs2233419AG were associated with a significantly increased risk of developing recurrent wheezing (p?=?0.04, p?=?0.04 and p?=?0.03), whereas TLR3-rs3775291TC was associated with a significantly reduced risk (p?=?0.03). Interestingly, the study of gene-environment interactions showed that rhinovirus was significantly associated with recurrent wheezing in the presence of IL4Ra-rs1801275GG and G (odds ratio [OR] 6.03, 95% confidence interval [CI]: 1.21-30.10, p?=?0.03) and MAP3K1-rs702689AA (OR 4.09, 95% CI: 1.14-14.61, p?=?0.03).This study shows a clear relationship between the risk of wheezing and polymorphisms of some genes involved in the immune response. Although further studies are needed to confirm the results, these findings may be useful for the early identification of children at the highest risk of developing recurrent episodes and possibly subsequent asthma.

SUBMITTER: Esposito S

PROVIDER: S-EPMC4210469 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Genetic polymorphisms and risk of recurrent wheezing in pediatric age.

Esposito Susanna S Ierardi Valentina V Daleno Cristina C Scala Alessia A Terranova Leonardo L Tagliabue Claudia C Rios Walter Peves WP Pelucchi Claudio C Principi Nicola N

BMC pulmonary medicine 20141018

<h4>Background</h4>Wheezing during early life is a very common disorder, but the reasons underlying the different wheezing phenotypes are still unclear. The aims of this study were to analyse the potential correlations between the risk of developing recurrent wheezing and the presence of specific polymorphisms of some genes regulating immune system function, and to study the relative importance of the associations of different viruses and genetic polymorphisms in causing recurrent episodes.<h4>M ...[more]

PMID: 25326706

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Project description:Asthma is one of the most common chronic diseases affecting children's health, and recurrent wheezing in infants is closely related to childhood asthma. However, up to now, there is a lack of unified diagnostic criteria and interventions for recurrent wheezing in infants. By analyzing and discussing the risk factors of recurrent wheezing in infants and related intervention measures, we aim to take individualized treatment for different children and reduce the occurrence of recurrent wheezing in infants. From January 2017 to December 2020, children under 3 years old who were admitted to the Department of Pediatric Respiratory of Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine with the chief complaint of wheezing for the first time and were clinically diagnosed with bronchiolitis, asthmatic bronchopneumonia and asthmatic bronchitis were retrospectively analyzed through telephone questionnaires. These children were divided into two groups based on whether the wheezing occurred again after discharge. The demographic characteristics, clinical treatment, imaging characteristics, and related interventions and outcomes after discharge were analyzed in both groups. Among the 523 children under 3 years old who were hospitalized due to wheezing, 264 (50.5%) did not have wheezing after discharge, and 259 (49.5%) still had wheezing after discharge. Both chi-squared test and multivariate analysis showed that male, history of eczema, history of rhinitis, history of wheezing before hospitalization, family smoke exposure, mycoplasma infection and inhalation allergen sensitization were risk factors for recurrent wheezing in infants and young children (P<0.05). Simultaneously, Cox survival curve showed that different intervention time and intervention methods would lead to different prognosis. (I) Male, with a history of eczema, rhinitis, wheezing before hospitalization, family environment smoke exposure, mycoplasma infection and a history of inhalation allergy are high risk factors for recurrent wheezing in the recurrent wheezing group, and are more likely to have recurrent wheezing after discharge, with shorter days of wheezing control; (II) there was a significant interaction between mycoplasma infection and a history of inhalation allergy in infants with the risk of recurrent wheezing; (III) long-term intervention for children with wheezing for 4 weeks or more after discharge can reduce the probability of recurrent wheezing; (IV) for children of male, with a history of eczema or rhinitis, the most effective intervention to reduce the probability of recurrent wheezing is long-term inhaled corticosteroids (ICS) treatment after discharge.

Project description:BackgroundPredicting which preschool children with recurrent wheezing (RW) will develop school-age asthma (SA) is difficult, highlighting the critical need to clarify the pathogenesis of RW and the mechanistic relationship between RW and SA. Despite shared environmental exposures and genetic determinants, RW and SA are usually studied in isolation. Based on network analysis of nasal and tracheal transcriptomes, we aimed to identify convergent transcriptomic mechanisms in RW and SA.MethodsRNA-sequencing data from nasal and tracheal brushing samples were acquired from the Gene Expression Omnibus. Combined with single-cell transcriptome data, cell deconvolution was used to infer the composition of 18 cellular components within the airway. Consensus weighted gene co-expression network analysis was performed to identify consensus modules closely related to both RW and SA. Shared pathways underlying consensus modules between RW and SA were explored by enrichment analysis. Hub genes between RW and SA were identified using machine learning strategies and validated using external datasets and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, the potential value of hub genes in defining RW subsets was determined using nasal and tracheal transcriptome data.ResultsCo-expression network analysis revealed similarities in the transcriptional networks of RW and SA in the upper and lower airways. Cell deconvolution analysis revealed an increase in mast cell fraction but decrease in club cell fraction in both RW and SA airways compared to controls. Consensus network analysis identified two consensus modules highly associated with both RW and SA. Enrichment analysis of the two consensus modules indicated that fatty acid metabolism-related pathways were shared key signals between RW and SA. Furthermore, machine learning strategies identified five hub genes, i.e., CST1, CST2, CST4, POSTN, and NRTK2, with the up-regulated hub genes in RW and SA validated using three independent external datasets and qRT-PCR. The gene signatures of the five hub genes could potentially be used to determine type 2 (T2)-high and T2-low subsets in preschoolers with RW.ConclusionsThese findings improve our understanding of the molecular pathogenesis of RW and provide a rationale for future exploration of the mechanistic relationship between RW and SA.

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Genetic polymorphisms and risk of recurrent wheezing in pediatric age.

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Genetic polymorphisms and risk of recurrent wheezing in pediatric age.

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