Dataset Information

Interactions between innate immunity genes and early-life risk factors in allergic rhinitis.

ABSTRACT:

Purpose

Allergic rhinitis (AR) is a common chronic disease. Many factors could affect the development of AR. We investigated early-life factors, such as delivery mode, feeding method, and use of antibiotics during infancy, which could affect the development of AR. In addition, how interactions between these factors and innate gene polymorphisms influence the development of AR was investigated.

Methods

A cross-sectional study of 1,828 children aged 9-12 years was conducted. Three early-life factors and AR were assessed by a questionnaire. Skin prick tests were done. Polymorphisms of TLR4 (rs1927911) and CD14 (rs2569190) were genotyped.

Results

Use of antibiotics during infancy increased the risk of AR (aOR [95% CI] 1.511 [1.222-2.037]) and atopic AR (aOR [95% CI], 1.565 [1.078-2.272]). There were synergistic interactions between caesarean delivery, formula feeding, and use of antibiotics in the rate of atopic AR (aOR [95% CI], 3.038 [1.256-7.347]). Additional analyses revealed that the risk for the development of AR or atopic AR subjects with the TLR4 CC genotype were highest when all the 3 early-life factors were present (aOR [95% CI], 5.127 [1.265-20.780] for AR; 6.078 [1.499-24.649] for atopic AR). In addition, the risk for the development of AR or atopic AR in subjects with the CD14 TT genotype were highest when all the 3 early-life factors were present (aOR [95% CI], 5.960 [1.421-15.002] for AR; 6.714 [1.440-31.312] for atopic AR).

Conclusions

Delivery mode, feeding method, and use of antibiotics during infancy appeared to have synergistic interactions in the development of AR. Gene-environment interactions between polymorphism of innate genes and early- life risk factors might affect the development of AR.

SUBMITTER: Seo JH

PROVIDER: S-EPMC4397364 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Interactions between innate immunity genes and early-life risk factors in allergic rhinitis.

Seo Ju Hee JH Kim Hyung Young HY Jung Young Ho YH Lee Eun E Yang Song I SI Yu Ho Sung HS Kim Young Joon YJ Kang Mi Jin MJ Kim Ha Jung HJ Park Kang Seo KS Kwon Ji Won JW Kim Byung Ju BJ Kim Hyo Bin HB Kim Eun Jin EJ Lee Joo Shil JS Lee So Yeon SY Hong Soo Jong SJ

Allergy, asthma & immunology research 20150318 3

<h4>Purpose</h4>Allergic rhinitis (AR) is a common chronic disease. Many factors could affect the development of AR. We investigated early-life factors, such as delivery mode, feeding method, and use of antibiotics during infancy, which could affect the development of AR. In addition, how interactions between these factors and innate gene polymorphisms influence the development of AR was investigated.<h4>Methods</h4>A cross-sectional study of 1,828 children aged 9-12 years was conducted. Three e ...[more]

PMID: 25840711

Similar Datasets

Project description:BackgroundRecent research has pointed out the important roles of epigenetic modifications in the development and persistence of allergic rhinitis (AR), especially in relation to DNA methylation of disease-associated genes. We investigated whether AR susceptibility genes were epigenetically regulated, and whether methylation modulation of these genes in response to early-life environment could be a molecular mechanism underlying the risk for AR onset in a cohort of children aged 3-6 years in China.MethodsPeripheral blood mononuclear cell (PBMC) samples were collected from 130 children patients, aged 3-6 years and diagnosed with AR; and 154 matched controls to detect promoter methylation in 25 AR susceptibility genes with the MethylTarget approach. Methylation levels were compared for each CpG site, each amplified region, and each gene. In addition, the relationship among DNA methylation, early-life environmental risk factors and AR onset were assessed.ResultsMaternal allergic history (P = 0.0390) and pet exposure (P = 0.0339) were significantly associated with increased AR risk. Differential methylation analyses were successfully performed for 507 CpG sites, 34 amplified regions and 17 genes and significant hypomethylation was observed in the promoter region of ADAM33 in AR patients [multiple test-corrected (FDR) P-value < 0.05]. Spearman correlation analysis revealed that the hypomethylation of ADAM33 was significantly associated with higher eosinophil counts (Spearman's ρ: - 0.187, P-value = 0.037). According to the results of the multiple regression analysis, after adjusting for cofounders, the interaction of early-life pet exposure with methylation level of ADAM33 increased the risk for AR onset 1.423 times more in children (95% CI = 0.0290-4.109, P-value = 0.005).ConclusionThis study provides evidence that early-life pet exposure and low methylation level of ADAM33 increase AR risk in children, and the interaction between pet exposure and methylation level of ADAM33 may play an important role in the development of AR.

Project description:BACKGROUND: Asthma genetics has been extensively studied and many genes have been associated with the development or severity of this disease. In contrast, the genetic basis of allergic rhinitis (AR) has not been evaluated as extensively. It is well known that asthma is closely related with AR since a large proportion of individuals with asthma also present symptoms of AR, and patients with AR have a 5-6 fold increased risk of developing asthma. Thus, the relevance of asthma candidate genes as predisposing factors for AR is worth investigating. The present study was designed to investigate if SNPs in highly replicated asthma genes are associated with the occurrence of AR. METHODS: A total of 192 SNPs from 21 asthma candidate genes reported to be associated with asthma in 6 or more unrelated studies were genotyped in a Swedish population with 246 AR patients and 431 controls. Genotypes for 429 SNPs from the same set of genes were also extracted from a Singapore Chinese genome-wide dataset which consisted of 456 AR cases and 486 controls. All SNPs were subsequently analyzed for association with AR and their influence on allergic sensitization to common allergens. RESULTS: A limited number of potential associations were observed and the overall pattern of P-values corresponds well to the expectations in the absence of an effect. However, in the tests of allele effects in the Chinese population the number of significant P-values exceeds the expectations. The strongest signals were found for SNPs in NPSR1 and CTLA4. In these genes, a total of nine SNPs showed P-values <0.001 with corresponding Q-values <0.05. In the NPSR1 gene some P-values were lower than the Bonferroni correction level. Reanalysis after elimination of all patients with asthmatic symptoms excluded asthma as a confounding factor in our results. Weaker indications were found for IL13 and GSTP1 with respect to sensitization to birch pollen in the Swedish population. CONCLUSIONS: Genetic variation in the majority of the highly replicated asthma genes were not associated to AR in our populations which suggest that asthma and AR could have less in common than previously anticipated. However, NPSR1 and CTLA4 can be genetic links between AR and asthma and associations of polymorphisms in NPSR1 with AR have not been reported previously.

Dataset Information

Interactions between innate immunity genes and early-life risk factors in allergic rhinitis.

Purpose

Methods

Results

Conclusions

Publications

Interactions between innate immunity genes and early-life risk factors in allergic rhinitis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets