A Meta-Analysis of IL-13 Polymorphisms and Pediatric Asthma Risk

Liu, Zhigang; Li, Peijie; Wang, JinRong; Fan, Qi-Wen; Yan, Ping; Zhang, Xiaojing; Han, Bo

doi:10.12659/msm.891017

Cited by 16 publications

(8 citation statements)

References 27 publications

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“…These asthma GWAS have used a range of asthma definitions, including physician diagnosis in GABRIEL, electronic medical record information in eMERGE, and physicians’ diagnosis and/or standardized questionnaires in the TAGC [ 4 , 24 , 47 ]. A number of prior GWAS have identified distinct genetic susceptibility for pediatric onset asthma, particularly implicating ORLDM3 / GSDMB , IL1RL1 , and IL13 , which were all found to have association with childhood asthma in the current analysis [ 4 , 5 , 6 , 7 , 24 , 59 ]. C11orf30-LRRC3 , which also has association in this GWAS, has been associated with in pediatric asthma previously, though in prior GWAS the primary link with asthma has been in the setting of allergic disease [ 33 , 60 ].…”

Section: Discussionmentioning

confidence: 94%

Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study

et al. 2018

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BackgroundChildhood asthma is strongly influenced by genetics and is a risk factor for reduced lung function and chronic obstructive pulmonary disease (COPD) in adults. This study investigates self-reported childhood asthma in adult smokers from the COPDGene Study. We hypothesize that childhood asthma is associated with decreased lung function, increased risk for COPD, and that a genome-wide association study (GWAS) will show association with established asthma variants.MethodsWe evaluated current and former smokers ages 45–80 of non-Hispanic white (NHW) or African American (AA) race. Childhood asthma was defined by self-report of asthma, diagnosed by a medical professional, with onset at < 16 years or during childhood. Subjects with a history of childhood asthma were compared to those who never had asthma based on lung function, development of COPD, and genetic variation. GWAS was performed in NHW and AA populations, and combined in meta-analysis. Two sets of established asthma SNPs from published literature were examined for association with childhood asthma.ResultsAmong 10,199 adult smokers, 730 (7%) reported childhood asthma and 7493 (73%) reported no history of asthma. Childhood asthmatics had reduced lung function and increased risk for COPD (OR 3.42, 95% CI 2.81–4.18). Genotype data was assessed for 8031 subjects. Among NHWs, 391(7%) had childhood asthma, and GWAS identified one genome-wide significant association in KIAA1958 (rs59289606, p = 4.82 × 10− 8). Among AAs, 339 (12%) had childhood asthma. No SNPs reached genome-wide significance in the AAs or in the meta-analysis combining NHW and AA subjects; however, potential regions of interest were identified. Established asthma SNPs were examined, seven from the NHGRI-EBI database and five with genome-wide significance in the largest pediatric asthma GWAS. Associations were found in the current childhood asthma GWAS with known asthma loci in IL1RL1, IL13, LINC01149, near GSDMB, and in the C11orf30-LRRC32 region (Bonferroni adjusted p < 0.05 for all comparisons).ConclusionsChildhood asthmatics are at increased risk for COPD. Defining asthma by self-report is valid in populations at risk for COPD, identifying subjects with clinical and genetic characteristics known to associate with childhood asthma. This has potential to improve clinical understanding of asthma-COPD overlap (ACO) and enhance future research into ACO-specific treatment regimens.Trial registrationClinicalTrials.gov, NCT00608764 (Active since January 28, 2008).Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0890-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 94%

Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study

et al. 2018

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“…For example, IREB2 gene rs2568494 polymorphism has been shown to be associated with susceptibility to chronic obstructive pulmonary disease [ 5 ]. IL13 gene polymorphisms contribute to the development of pediatric asthma [ 6 ]. The human leukocyte antigen (HLA) super-locus is a genomic region in chromosome position 6p21 that encodes the 6 classical transplantation HLA genes and at least 132 protein-coding genes that have important roles in the regulation of the immune system, as well as some other fundamental molecular and cellular processes [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Association of HLA-DRB1 Gene Polymorphism with Risk of Asthma: A Meta-Analysis

Yao

Zhu

et al. 2016

Med Sci Monit Basic Res

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BackgroundThe relationship between HLA-DRB1 alleles and asthma is controversial. The purpose of this study was to evaluate the relationship between HLA-DRB1 alleles and risk of asthma.Material/MethodsWe searched PubMed, Chinese National Knowledge Infrastructure (CNKI), Wan Fang (Chinese) database, and Chinese Biomedical Medical databases (CBM) to find studies on the relationship between HLA-DRB1 alleles and risk of asthma. We calculated the pooled odds ratio (OR) and 95% confidence interval (CI) using STATA 12.0. Finally, a total of 24 studies were included in this meta-analysis.ResultsThe results revealed that DRB1*03 was positively associated with risk of asthma (OR=1.51, 95%CI=1.27–1.80), and DRB1*15 was negatively associated with risk of asthma (OR=0.63, 95%CI=0.42–0.93), but no association was found in other HLA-DRB1 alleles. Subgroup analysis by age revealed that DRB1*03, DRB1*04, DRB1*09, and DRB1*15 were associated with asthma in children. Subgroup analysis by ethnicity showed that DRB1*03 and DRB1*15 were associated with asthma in whites, and DRB1*07 and DRB1*14 were associated with asthma in Asians.ConclusionsThis results of this meta-analysis suggest that HLA-DRB1 alleles are associated with asthma.

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“…It is important to highlight the strengths of our meta-analysis and acknowledge its weaknesses. The central advantage of this meta-analysis is the rigorous statistical review of data from the literature that cannot be achieved by any single study [ 38 – 40 ]. An unambiguous and strong association between DEFB1 SNPs and digestive diseases cannot be drawn from the results of a single study, but our approach confirmed this relationship by analyzing the results from multiple studies.…”

Section: Discussionmentioning

confidence: 99%

Association between Genetic Polymorphisms in DEFB1 and Susceptibility to Digestive Diseases

Huang

Wang

et al. 2015

Med Sci Monit

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BackgroundAberrant expression of defensins is implicated in the pathogenesis of digestive diseases. However, the contribution of specific defensins and the influence of their genetic polymorphisms on the progression of digestive diseases remain controversial. In the present meta-analysis, we investigated the association between DEFB1 SNPs and the susceptibility to digestive diseases.Material/MethodsCase-control studies that reported the correlation between DEFB1 SNPs and the susceptibility to digestive diseases were identified through electronic databases searches, and high-quality studies that satisfied our inclusion criteria were selected for this meta-analysis. Statistical analyses were performed utilizing STATA software version 12.0.ResultsThe present meta-analysis revealed that patients with digestive diseases exhibited higher frequencies of the DEFB1 genetic variants rs11362G>A, rs1800972C>G, and rs1799946G>A compared to healthy controls under the allele model. Subgroup analysis based on country showed that the rs1800972C>G variant under allele model and rs1799946G>A are associated with the susceptibility to digestive diseases in Hungarian and Italian populations, respectively. Subgroup analysis based on disease type showed that: (1) rs11362G>A variant was strongly associated with severe acute pancreatitis (SAP) and chronic gastritis, (2) frequency of rs1800972C>G variant was higher in SAP subgroup, and (3) frequency of rs1799946G>A variant was positively associated with the susceptibility to Crohn’s disease (CD) under the allele model and with SAP.ConclusionsOur meta-analysis provides evidence that DEFB1 genetic polymorphisms rs11362G>A, rs1800972C>G and rs1799946G>A are important contributing factors to the development of digestive diseases.

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A Meta-Analysis of IL-13 Polymorphisms and Pediatric Asthma Risk

Cited by 16 publications

References 27 publications

Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study

Childhood asthma is associated with COPD and known asthma variants in COPDGene: a genome-wide association study

Association of HLA-DRB1 Gene Polymorphism with Risk of Asthma: A Meta-Analysis

Association between Genetic Polymorphisms in DEFB1 and Susceptibility to Digestive Diseases

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