title: Human leukocyte antigen class II variants and adult-onset asthma: does occupational allergen exposure play a role?
abstract: Recently, a locus centred on rs9273349 in the HLA-DQ region emerged from genome-wide association studies of adult-onset asthma. We aimed to further investigate the role of human leukocyte antigen (HLA) class II in adult-onset asthma and a possible interaction with occupational exposures. We imputed classical HLA-II alleles from 7579 single-nucleotide polymorphisms in 6025 subjects (1202 with adult-onset asthma) from European cohorts: ECRHS, SAPALDIA, EGEA and B58C, and from surveys of bakers and agricultural workers. Based on an asthma-specific job-exposure matrix, 2629 subjects had ever been exposed to high molecular weight (HMW) allergens. We explored associations between 23 common HLA-II alleles and adult-onset asthma, and tested for gene-environment interaction with occupational exposure to HMW allergens. Interaction was also tested for rs9273349. Marginal associations of classical HLA-II alleles and adult-onset asthma were not statistically significant. Interaction was detected between the DPB1*03:01 allele and exposure to HMW allergens (p = 0.009), in particular to latex (p = 0.01). In the unexposed group, the DPB1*03:01 allele was associated with adult-onset asthma (OR 0.67, 95%CI 0.53-0.86). HMW allergen exposures did not modify the association of rs9273349 with adult-onset asthma. Common classical HLA-II alleles were not marginally associated with adult-onset asthma. The association of latex exposure and adult-onset asthma may be modified by DPB1*03:01.
authors.affiliation: For the authors' affiliations see the Acknowledgements section l.a.smit@uu.nl.
authors.forename: Lidwien A M
authors.initials: LA
authors.lastname: Smit
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Roel
authors.initials: R
authors.lastname: Vermeulen
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Florence
authors.initials: F
authors.lastname: Demenais
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Orianne
authors.initials: O
authors.lastname: Dumas
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Anne-Elie
authors.initials: AE
authors.lastname: Carsin
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Paul
authors.initials: P
authors.lastname: Cullinan
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Ivan
authors.initials: I
authors.lastname: Curjuric
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Ghosh
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Dick
authors.initials: D
authors.lastname: Heederik
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Medea
authors.initials: M
authors.lastname: Imboden
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Deborah
authors.initials: D
authors.lastname: Jarvis
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Nicole
authors.initials: N
authors.lastname: Le Moual
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Amar
authors.initials: A
authors.lastname: Mehta
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: David
authors.initials: D
authors.lastname: Miedinger
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Torben
authors.initials: T
authors.lastname: Sigsgaard
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Valérie
authors.initials: V
authors.lastname: Siroux
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: David
authors.initials: D
authors.lastname: Vernez
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Jan Paul
authors.initials: JP
authors.lastname: Zock
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Francine
authors.initials: F
authors.lastname: Kauffmann
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Nicole
authors.initials: N
authors.lastname: Probst-Hensch
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.affiliation: For the authors' affiliations see the Acknowledgements section.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bouzigon
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D000485:Allergens / Q000276:immunology*; D001249:Asthma / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D015331:Cohort Studies; D005060:Europe; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains / Q000235:genetics; D059811:HLA-DRB1 Chains / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D016273:Occupational Exposure; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D000485:Allergens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II