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  • Title: Human leukocyte antigen class II variants and adult-onset asthma: does occupational allergen exposure play a role?
    Author: Smit LA, Strachan DP, Vermeulen R, de Bakker PI, Demenais F, Dumas O, Carsin AE, Cullinan P, Curjuric I, Ghosh RE, Heederik D, Imboden M, Jarvis D, Lathrop M, Le Moual N, Mehta A, Miedinger D, Sigsgaard T, Siroux V, Vernez D, Zock JP, Kauffmann F, Probst-Hensch N, Kogevinas M, Bouzigon E.
    Journal: Eur Respir J; 2014 Nov; 44(5):1234-42. PubMed ID: 25034568.
    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.
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