Format

Send to

Choose Destination
See comment in PubMed Commons below
Clin Exp Allergy. 2012 Feb;42(2):229-37. doi: 10.1111/j.1365-2222.2011.03874.x.

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

Author information

1
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. supinda@post.harvard.edu

Abstract

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.

Comment in

PMID:
22010907
PMCID:
PMC3353543
DOI:
10.1111/j.1365-2222.2011.03874.x
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley Icon for PubMed Central
    Loading ...
    Support Center