Gene-by-environment effect of house dust mite on purinergic receptor P2Y12 (P2RY12) and lung function in children with asthma.

Authors: Bunyavanich, S  Boyce, JA  Raby, BA  Weiss, ST 
Citation: Bunyavanich S, etal., Clin Exp Allergy. 2012 Feb;42(2):229-37.
Pubmed: (View Article at PubMed) PMID:22010907
DOI: Full-text: DOI:10.1111/j.1365-2222.2011.03874.x

BACKGROUND: Distinct receptors likely exist for leukotriene (LT)E(4), a potent mediator of airway inflammation. Purinergic receptor P2Y12 is needed for LTE(4)-induced airways inflammation, and P2Y12 antagonism attenuates house dust mite-induced pulmonary eosinophilia in mice. Although experimental data support a role for P2Y12 in airway inflammation, its role in human asthma has never been studied. OBJECTIVE: To test for association between variants in the P2Y12 gene (P2RY12) and lung function in human subjects with asthma, and to examine for gene-by-environment interaction with house dust mite exposure. METHODS: Nineteen single nucleotide polymorphisms (SNPs) in P2RY12 were genotyped in 422 children with asthma and their parents (n = 1266). Using family based methods, we tested for associations between these SNPs and five lung function measures. We performed haplotype association analyses and tested for gene-by-environment interactions using house dust mite exposure. We used the false discovery rate to account for multiple comparisons. RESULTS: Five SNPs in P2RY12 were associated with multiple lung function measures (P-values 0.006-0.025). Haplotypes in P2RY12 were also associated with lung function (P-values 0.0055-0.046). House dust mite exposure modulated associations between P2RY12 and lung function, with minor allele homozygotes exposed to house dust mite demonstrating worse lung function than those unexposed (significant interaction P-values 0.0028-0.040). CONCLUSIONS AND CLINICAL RELEVANCE: The P2RY12 variants were associated with lung function in a large family-based asthma cohort. House dust mite exposure caused significant gene-by-environment effects. Our findings add the first human evidence to experimental data supporting a role for P2Y12 in lung function. P2Y12 could represent a novel target for asthma treatment.


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CRRD Object Information
CRRD ID: 6480532
Created: 2012-03-27
Species: All species
Last Modified: 2012-03-27
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.