Genome-wide interaction study of dust mite allergen on lung function in children with asthma.
BACKGROUND
Childhood asthma is likely the result of gene-by-environment (G × E) interactions. Dust mite is a known risk factor for asthma morbidity. Yet, there have been no genome-wide G × E studies of dust mite allergen on asthma-related phenotypes.


OBJECTIVE
We sought to identify genetic variants whose effects on lung function in children with asthma are modified by the level of dust mite allergen exposure.


METHODS
A genome-wide interaction analysis of dust mite allergen level and lung function was performed in a cohort of Puerto Rican children with asthma (Puerto Rico Genetics of Asthma and Lifestyle [PRGOAL]). Replication was attempted in 2 independent cohorts, the Childhood Asthma Management Program (CAMP) and the Genetics of Asthma in Costa Rica Study.


RESULTS
Single nucleotide polymorphism (SNP) rs117902240 showed a significant interaction effect on FEV1with dust mite allergen level in PRGOAL (interaction P = 3.1 × 10-8), and replicated in the same direction in CAMP white children and CAMP Hispanic children (combined interaction P = .0065 for replication cohorts and 7.4 × 10-9for all cohorts). Rs117902240 was positively associated with FEV1in children exposed to low dust mite allergen levels, but negatively associated with FEV1in children exposed to high levels. This SNP is on chromosome 8q24, adjacent to a binding site for CCAAT/enhancer-binding protein beta, a transcription factor that forms part of the IL-17 signaling pathway. None of the SNPs identified for FEV1/forced vital capacity replicated in the independent cohorts.


CONCLUSIONS
Dust mite allergen exposure modifies the estimated effect of rs117902240 on FEV1in children with asthma. Analysis of existing data suggests that this SNP may have transcription factor regulatory functions.
Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pa; University of Pittsburgh School of Medicine, Pittsburgh, Pa.
Erick
E
Forno
Channing Division of Network Medicine, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, Mass.
Joanne
J
Sordillo
Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pa; University of Pittsburgh School of Medicine, Pittsburgh, Pa.
John
J
Brehm
Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pa; University of Pittsburgh School of Medicine, Pittsburgh, Pa.
Wei
W
Chen
University of Pittsburgh School of Medicine, Pittsburgh, Pa.
Takis
T
Benos
Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pa; University of Pittsburgh School of Medicine, Pittsburgh, Pa.
Qi
Q
Yan
Department of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica.
Lydiana
L
Avila
Department of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica.
Manuel
M
Soto-Quirós
Department of Pediatrics, University of Connecticut Health Center, Farmington, Conn.
Michelle M
MM
Cloutier
Department of Pediatrics, University of Puerto Rico, San Juan, Puerto Rico.
Angel
A
Colón-Semidey
Department of Pediatrics, University of Puerto Rico, San Juan, Puerto Rico.
Maria
M
Alvarez
Behavioral Sciences Research Institute, University of Puerto Rico, San Juan, Puerto Rico.
Edna
E
Acosta-Pérez
Channing Division of Network Medicine, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, Mass.
Scott T
ST
Weiss
Channing Division of Network Medicine, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, Mass.
Augusto A
AA
Litonjua
Behavioral Sciences Research Institute, University of Puerto Rico, San Juan, Puerto Rico.
Glorisa
G
Canino
Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pa; University of Pittsburgh School of Medicine, Pittsburgh, Pa. Electronic address: juan.celedon@chp.edu.
Juan C
JC
Celedón
D000293:Adolescent; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D001249:Asthma / Q000276:immunology*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005260:Female; D059647:Gene-Environment Interaction; D055106:Genome-Wide Association Study; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D008168:Lung / Q000502:physiology*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011485:Protein Binding; D011647:Puerto Rico; D012129:Respiratory Function Tests
D039741:Antigens, Dermatophagoides; D022762:CCAAT-Enhancer-Binding Proteins; D020381:Interleukin-17
CEBPβ; Childhood asthma; dust mite allergen; gene-by-environment interactions; genome-wide interaction study; lung function