A polymorphism controlling ORMDL3 expression is associated with asthma that is poorly controlled by current medications

Roger Tavendale, Donald F. Macgregor, Somnath Mukhopadhyay, Colin N. A. Palmer (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    126 Citations (Scopus)

    Abstract

    Background: The specific genetic contributions to childhood asthma have been difficult to elucidate. A recent whole-genome association study suggested that single nucleotide polymorphisms at loci controlling the expression of the ORMDL3 gene and others in the neighborhood of the NRG1 and ERO1LB genes might be important.

    Objective: We sought to replicate the associations of these genetic markers with asthma in a large population of asthmatic patients from Scotland and to assess the effect of these variants on asthma outcomes.

    Methods: Using mouthwash-derived DNA and clinical interviews and measurements, we investigated the association of 3 single nucleotide polymorphisms in the candidate genes with susceptibility to asthma in a case-control study and also exacerbations in a group of 1054 patients aged 3 to 22 years.

    Results: A common C/T polymorphism at a locus controlling ORMDL3 gene expression (rs7216389) was significantly associated with the risk of childhood asthma (P = 1.73 x 10(-12)), with a single copy of the T allele conferring an odds ratio of 1.50 (95% CI, 1.24-1.81) and 2 copies of the T allele conferring an odds ratio of 2.11 (95% CI, 1.71-2.61), respectively. In asthmatic patients the T allele was associated with exacerbations of the condition (P = .008). Polymorphisms at the loci of nearby genes for NRG1 (rs4512342) and ERO1LB (rs10924993) were associated with neither the occurrence of nor exacerbations of asthma.

    Conclusion: A common genetic variation at a locus controlling the expression of the ORMDL3 locus increases the susceptibility to asthma and is associated with poor control of the condition in children and young adults.

    Original languageEnglish
    Pages (from-to)860-863
    Number of pages4
    JournalJournal of Allergy and Clinical Immunology
    Volume121
    Issue number4
    DOIs
    Publication statusPublished - Apr 2008

    Keywords

    • asthma
    • ORMDL3
    • genetics
    • single nucleotide polymorphism
    • susceptibility
    • exacerbation
    • GENOME-WIDE ASSOCIATION
    • SUSCEPTIBILITY GENES
    • ATOPIC-DERMATITIS
    • CHILDHOOD ASTHMA
    • PPARG LOCUS
    • RISK
    • EXACERBATIONS
    • FILAGGRIN
    • VARIANTS
    • GENOTYPE

    Cite this