Fungal exposure modulates the effect of polymorphisms of chitinases on emergency department visits and hospitalizations.
BACKGROUND
Chitinases are enzymes that cleave chitin, which is present in fungal cells. Two types of human chitinases, chitotriosidase and acidic mammalian chitinase, and the chitinase-like protein, YKL-40, seem to play an important role in asthma. We hypothesized that exposure to environmental fungi may modulate the effect of chitinases in individuals with asthma.


OBJECTIVE
To explore whether interactions between high fungal exposure and common genetic variants in the two chitinases in humans, CHIT1 and CHIA, and the chitinase 3-like 1 gene, CHI3L1, are associated with severe asthma exacerbations and other asthma-related outcomes.


METHODS
Forty-eight single nucleotide polymorphisms (SNPs) in CHIT1, CHIA, and CHI3L1 and one CHIT1 duplication were genotyped in 395 subjects and their parents as part of the Childhood Asthma Management Program. Household levels of mold (an index of fungal exposure) were determined on house dust samples. We conducted family-based association tests with gene-environment interactions. Our outcome was severe exacerbation, defined as emergency department visits and hospitalizations from asthma over a 4-year period, and our secondary outcomes included indices of lung function and allergy-related phenotypes.


RESULTS
Of the 395 subjects who had mold levels at randomization, 24% (95 subjects) had levels that were greater than 25,000 units per gram of house dust (high mold exposure). High mold exposure significantly modified the relation between three SNPs in CHIT1 (rs2486953, rs4950936, and rs1417149) and severe exacerbations (P for interaction 0.0010 for rs2486953, 0.0008 for rs4950936, and 0.0005 for rs1417149). High mold exposure did not significantly modify the relationship between any of the other variants and outcomes.


CONCLUSIONS
Environmental exposure to fungi, modifies the effect of CHIT1 SNPs on severe asthma exacerbations.
Department of Population Medicine, Harvard Pilgrim Health Care Institute and Harvard Medical School, Boston, Massachusetts, USA. ann.wu@childrens.harvard.edu
Ann Chen
AC
Wu
Jessica
J
Lasky-Su
Christine A
CA
Rogers
Barbara J
BJ
Klanderman
Augusto A
AA
Litonjua
D054392:Adipokines; D001249:Asthma / Q000235:genetics*; D002648:Child; D000071451:Chitinase-3-Like Protein 1; D002688:Chitinases / Q000235:genetics* / Q000378:metabolism; D004306:Dose-Response Relationship, Immunologic; D004391:Dust / Q000276:immunology; D004781:Environmental Exposure / Q000009:adverse effects*; D005192:Family Health; D005260:Female; D005658:Fungi / Q000276:immunology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006596:Hexosaminidases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
D054392:Adipokines; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D004391:Dust; D006023:Glycoproteins; D037102:Lectins; D006596:Hexosaminidases; C086400:chitotriosidase; C499254:CHIA protein, human; D002688:Chitinases