Dataset Information

Variants in TGFB1, dust mite exposure, and disease severity in children with asthma.

ABSTRACT:

Rationale

Polymorphisms in the gene for transforming growth factor-beta1 (TGFB1) have been associated with asthma, but not with airway responsiveness or disease exacerbations in subjects with asthma.

Objectives

To test for association between single nucleotide polymorphisms (SNPs) in TGFB1 and markers of asthma severity in childhood.

Methods

We tested for the association between nine SNPs in TGFB1 and indicators of asthma severity (lung function, airway responsiveness, and disease exacerbations) in two cohorts: 416 Costa Rican parent-child trios and 465 families of non-Hispanic white children in the Childhood Asthma Management Program (CAMP). We also tested for the interaction between these polymorphisms and exposure to dust mite allergen on asthma severity.

Measurements and main results

The A allele of promoter SNP rs2241712 was associated with increased airway responsiveness in Costa Rica (P = 0.0006) and CAMP (P = 0.005), and the C allele of an SNP in the promoter region (rs1800469) was associated with increased airway responsiveness in both cohorts (P ConclusionsSNPs in TGFB1 are associated with airway responsiveness and disease exacerbations in children with asthma. Moreover, dust mite exposure may modify the effect of TGFB1 SNPs on airway responsiveness and asthma exacerbations.

SUBMITTER: Sharma S

PROVIDER: S-EPMC2648908 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Publications

Variants in TGFB1, dust mite exposure, and disease severity in children with asthma.

Sharma Sunita S Raby Benjamin A BA Hunninghake Gary M GM Soto-Quirós Manuel M Avila Lydiana L Murphy Amy J AJ Lasky-Su Jessica J Klanderman Barbara J BJ Sylvia Jody S JS Weiss Scott T ST Celedón Juan C JC

American journal of respiratory and critical care medicine 20081218 5

<h4>Rationale</h4>Polymorphisms in the gene for transforming growth factor-beta1 (TGFB1) have been associated with asthma, but not with airway responsiveness or disease exacerbations in subjects with asthma.<h4>Objectives</h4>To test for association between single nucleotide polymorphisms (SNPs) in TGFB1 and markers of asthma severity in childhood.<h4>Methods</h4>We tested for the association between nine SNPs in TGFB1 and indicators of asthma severity (lung function, airway responsiveness, and ...[more]

PMID: 19096005

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Project description:Asthma is a chronic inflammatory disorder of the airways. Disease presentation varies greatly in terms of cause, development, severity, and response to medication, and thus the condition has been subdivided into a number of asthma phenotypes. There is still an unmet need for the identification of phenotype-specific markers and accompanying molecular tools that facilitate the classification of asthma phenotype. To this end, we utilised a range of molecular tools to characterise a well-defined group of female adults with poorly controlled atopic asthma associated with house dust mite (HDM) allergy, relative to non-asthmatic control subjects. Circulating messenger RNA (mRNA) and microRNA (miRNA) were sequenced and quantified, and a differential expression analysis of the two RNA populations performed to determine how gene expression and regulation varied in the disease state. Further, a number of circulating proteins (IL-4, 5, 10, 13, 17 A, Eotaxin, GM-CSF, IFNy, MCP-1, TARC, TNFα, Total IgE, and Endotoxin) were quantified to determine whether the protein profiles differed significantly dependent on disease state. Finally, we utilised a previously published assessment of the circulating "blood microbiome" performed using 16S rRNA amplification and sequencing. Asthmatic subjects displayed a range of significant alterations to circulating gene expression and regulation, relative to healthy control subjects, that may influence systemic immune activity. Notably, several circulating mRNAs were detected in just the asthma group or just in the control group, and many more were observed to be expressed at significantly different levels in the asthma group compared to the control group. Proteomic analysis revealed increased levels of inflammatory proteins within the serum, and decreased levels of the bacterial endotoxin protein in the asthmatic state. Comparison of blood microbiome composition revealed a significant increase in the Firmicutes phylum with asthma that was associated with a concomitant reduction in the Proteobacteria phylum. This study provides a valuable insight into the systemic changes evident in the HDM-associated asthma, identifies a range of molecules that are present in the circulation in a condition-specific manner (with clear biomarker potential), and highlights a range of hypotheses for further study.

Dataset Information

Variants in TGFB1, dust mite exposure, and disease severity in children with asthma.

Rationale

Objectives

Methods

Measurements and main results

Publications

Variants in TGFB1, dust mite exposure, and disease severity in children with asthma.

Similar Datasets

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