A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order

Respiratory Epidemiology and Public Health, Imperial College, London, United Kingdom.
The Journal of allergy and clinical immunology (Impact Factor: 11.25). 11/2011; 128(5):996-1005. DOI: 10.1016/j.jaci.2011.08.030
Source: PubMed

ABSTRACT Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear.
We sought to identify common genetic variant associations with prevalent AR and grass sensitization using existing genome-wide association study (GWAS) data and to determine whether genetic variants modify the protective effect of older siblings.
Approximately 2.2 million genotyped or imputed single nucleotide polymorphisms were investigated in 4 large European adult cohorts for AR (3,933 self-reported cases vs 8,965 control subjects) and grass sensitization (2,315 cases vs 10,032 control subjects).
Three loci reached genome-wide significance for either phenotype. The HLA variant rs7775228, which cis-regulates HLA-DRB4, was strongly associated with grass sensitization and weakly with AR (P(grass) = 1.6 × 10(-9); P(AR) = 8.0 × 10(-3)). Variants in a locus near chromosome 11 open reading frame 30 (C11orf30) and leucine-rich repeat containing 32 (LRRC32), which was previously associated with atopic dermatitis and eczema, were also strongly associated with both phenotypes (rs2155219; P(grass) = 9.4 × 10(-9); P(AR) = 3.8 × 10(-8)). The third genome-wide significant variant was rs17513503 (P(grass) = 1.2 × 10(-8); PAR = 7.4 × 10(-7)) which was located near transmembrane protein 232 (TMEM232) and solute carrier family 25, member 46 (SLC25A46). Twelve further loci with suggestive associations were also identified. Using a candidate gene approach, where we considered variants within 164 genes previously thought to be important, we found variants in 3 further genes that may be of interest: thymic stromal lymphopoietin (TSLP), Toll-like receptor 6 (TLR6) and nucleotide-binding oligomerization domain containing 1 (NOD1/CARD4). We found no evidence for variants that modified the effect of birth order on either phenotype.
This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses.

  • Source
    Journal of Investigative Dermatology 02/2012; 132(5):1505-7. DOI:10.1038/jid.2011.471 · 6.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this review is to highlight recently published important articles on upper airway diseases and allergen immunotherapy. We review articles on rhinitis, sinusitis, conjunctivitis, and immunotherapy. New insights into epidemiology, pathophysiology, diagnosis, and therapy are described for each of the above diseases.
    The Journal of allergy and clinical immunology 03/2012; 129(3):646-52. DOI:10.1016/j.jaci.2012.01.050 · 11.25 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Pollinosis, the generic name of pollen-induced allergies, classically involves the ORL (rhinitis and/or conjunctivitis) and pulmonary (asthma) fields, but also cutaneous reactions (eczema, urticaria and types of edema) may also occur. The pathophysiology of pollinosis, a multi-factorial illness, is not completely understood. The outcome of the host-pollen interaction is influenced by endogenous factors (genetic susceptibility as reflected by abnormal functional responses of the different cellular populations involved, the status of the tissue barriers, and the global status of the immune defense mechanism) and exogenous factors (properties of the pollen grains, the influence of gaseous and/or particulate pollutants, and the influence of commensal or pathogenic microorganisms). At the sub-cellular level, mitochondria have recently been shown to play a role in the pathophysiology of pollinosis, both as sources of energy for mast cell degranulation and during pro-allergic signaling through reactive oxygen species. We will review certain immunological, genetic and environmental aspects which are today essential for the diagnosis and management of pollinosis.
    Revue Française d'Allergologie 04/2012; 52(3):189–193. DOI:10.1016/j.reval.2012.01.017 · 0.35 Impact Factor
Show more