Human leukocyte antigen class II variants and adult-onset asthma: does occupational allergen exposure play a role?

Smit, Lidwien A M; Strachan, David P.; Vermeulen, Roel; Bakker, Paul I. W. de; Demenais, Florence; Dumas, Orianne; Carsin, Anne-Elie; Cullinan, Paul; Ivan, Cristina; Ghosh, Rebecca; Heederik, Dick; Imboden, Medea; Jarvis, Déborah; Lathrop, Mark; Moual, Nicole Le; Mehta, Amar; Malka, David; Sigsgaard, Torben; Siroux, Valérie; Vernez, David; Zock, Jan Paul; Kauffmann, F.; Probst-Hensch, Nicole; Kogevinas, Manolis

doi:10.1183/09031936.00068014

Cited by 10 publications

(12 citation statements)

References 40 publications

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“…As described above, because of the pivotal role of HLA-II molecules in the presentation of allergen-derived peptides, HLA alleles have been extensively studied in hypothesis-driven candidate gene association studies for allergic sensitization and asthma [38]. However, only a few studies have evaluated the association between HLA and nonallergic asthma, the pathogenesis of which has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Allergic and Nonallergic Asthma Have Distinct Phenotypic and Genotypic Features

Takejima

Agondi²,

Rodrigues³

et al. 2017

Int Arch Allergy Immunol

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Background: Identification of asthma phenotypes enables a better understanding and management of this heterogeneous disease. Studies have reported associations between human leukocyte antigens (HLA) and asthma in different populations, but the results have been inconclusive and they have rarely considered the distinct disease phenotypes. Our objective was to characterize allergic and nonallergic asthma phenotypes and evaluate possible associations with the HLA system. Methods: A total of 109 patients with asthma were prospectively followed during 2 years. They were divided into 2 groups, i.e., allergic and nonallergic asthma, according to their clinical history and skin prick test and serum-specific immunoglobulin E (IgE) results. The control group comprised 297 deceased donors of solid organs. Patients' features and HLA class I and II genotypes were assessed and compared. Results: This study showed different features between asthma phenotypes. Nonallergic patients were older at the onset of asthma symptoms and had a higher rate of intolerance to nonsteroidal anti-inflammatory drugs. Allergic patients had higher total serum IgE levels, reported atopic dermatitis and rhinoconjunctivitis more frequently, and, unexpectedly, had a greater disease severity. New associations between the HLA genotypes and allergic and nonallergic asthma were identified. The HLA-B*42, HLA-C*17, HLA-DPA1*03, and HLA-DPB1*105 genotypes were associated with allergic asthma and the HLA-B*48 genotype with the nonallergic phenotype. The presence of the haplotype HLA-DPA1*03 DQA*05 was associated with allergic asthma, and the presence of HLA-DPA1*03 and the absence of HLA-DQA*05 with nonallergic asthma. Conclusions: Allergic and nonallergic asthma have distinct phenotypic and genotypic features. New associations between asthma phenotypes and HLA class I and II were identified.

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Section: Introductionmentioning

confidence: 99%

Allergic and Nonallergic Asthma Have Distinct Phenotypic and Genotypic Features

Takejima

Agondi²,

Rodrigues³

et al. 2017

Int Arch Allergy Immunol

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“…All three cohorts used comparable study designs and highly comparable questionnaires. Participants included in the analyses were derived from the entire study population for EGEA and from the nested case–control samples within the ECRHS ( Smit et al 2014 ) and SAPALDIA cohorts ( Curjuric et al 2012 ). Participants had genome-wide SNP data; occupational history regarding LMW agents and irritants, particularly cleaning/disinfecting products; and data on adult-onset asthma and relevant covariates such as age, sex, and smoking status.…”

Section: Methodsmentioning

confidence: 99%

“…In all cohorts, current asthma was defined as ever diagnosis of asthma ( Moffatt et al 2010 ; Smit et al 2014 ) and presence of respiratory symptoms (wheeze; nocturnal chest tightness; attacks of breathlessness after activity, at rest, or at night; asthma attacks) or using asthma medications in the last 12 months. Participants without asthma were those without asthma at baseline and at follow-up.…”

Section: Methodsmentioning

confidence: 99%

“…The three ESE cohorts were pooled to increase statistical power as before ( Smit et al 2012 , 2014 ); this strategy also allowed us to assess the consistency of the results across cohorts. SNP–occupational exposure interactions were investigated using a logistic regression model that included the SNP effect assumed to be additive, a binary exposure (E) variable (1 = exposed, 0 = unexposed), and a multiplicative term for SNP × E interaction.…”

Section: Methodsmentioning

confidence: 99%

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Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies

Rava

Ahmed

Kogevinas

et al. 2017

Environ Health Perspect

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Background:The biological mechanisms by which cleaning products and disinfectants—an emerging risk factor—affect respiratory health remain incompletely evaluated. Studying genes by environment interactions (G × E) may help identify new genes related to adult-onset asthma.Objectives:We identified interactions between genetic polymorphisms of a large set of genes involved in the response to oxidative stress and occupational exposures to low molecular weight (LMW) agents or irritants on adult-onset asthma.Methods:Our data came from three large European cohorts: Epidemiological Family-based Study of the Genetics and Environment of Asthma (EGEA), Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults (SAPALDIA), and European Community Respiratory Health Survey in Adults (ECRHS). A candidate pathway–based strategy identified 163 genes involved in the response to oxidative stress and potentially related to exposures to LMW agents/irritants. Occupational exposures were evaluated using an asthma job-exposure matrix and job-specific questionnaires for cleaners and healthcare workers. Logistic regression models were used to detect G × E interactions, adjusted for age, sex, and population ancestry, in 2,599 adults (mean age, 47 years; 60% women, 36% exposed, 18% asthmatics). p-Values were corrected for multiple comparisons.Results:Ever exposure to LMW agents/irritants was associated with current adult-onset asthma [OR = 1.28 (95% CI: 1.04, 1.58)]. Eight single nucleotide polymorphism (SNP) by exposure interactions at five loci were found at p < 0.005: PLA2G4A (rs932476, chromosome 1), near PLA2R1 (rs2667026, chromosome 2), near RELA (rs931127, rs7949980, chromosome 11), PRKD1 (rs1958980, rs11847351, rs1958987, chromosome 14), and PRKCA (rs6504453, chromosome 17). Results were consistent across the three studies and after accounting for smoking.Conclusions:Using a pathway-based selection process, we identified novel genes potentially involved in adult asthma by interaction with occupational exposure. These genes play a role in the NF-κB pathway, which is involved in inflammation.Citation:Rava M, Ahmed I, Kogevinas M, Le Moual N, Bouzigon E, Curjuric I, Dizier MH, Dumas O, Gonzalez JR, Imboden M, Mehta AJ, Tubert-Bitter P, Zock JP, Jarvis D, Probst-Hensch NM, Demenais F, Nadif R. 2017. Genes interacting with occupational exposures to low molecular weight agents and irritants on adult-onset asthma in three European studies. Environ Health Perspect 125:207–214; http://dx.doi.org/10.1289/EHP376

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“…HLA also controls the secretion of cytokines and modulates the immune response by cytokine genes on haplotypes. Susceptibility alleles on HLA may also lead to GD/HT by preferentially regulating the Th2/Th1 pathways, respectively [7–10]. …”

Section: Cytokines and Cytokine-related Genes In Aitdmentioning

confidence: 99%

General and Specific Genetic Polymorphism of Cytokines-Related Gene in AITD

Xiaoheng

Mei²,

et al. 2017

Mediators of Inflammation

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Autoimmune thyroid disease (AITD) shows the highest incidence among organ-specific autoimmune diseases and is the most common thyroid disease in humans, including Graves' disease (GD) and Hashimoto's thyroiditis (HT). The susceptibility to autoimmune diseases is affected by increased autoantibody levels, susceptibility gene polymorphisms, environmental factors, and psychological factors, but the pathogenesis remains unclear. Various cytokines and related genes encoding them play important roles in the development and progression of AITD. CD152, an expression product of the CTLA-4 gene, downregulates T cell activation. The A/A genotype polymorphism in the CT60 locus may reduce the production of thyroid autoantibodies. The C1858T polymorphism of the PTNP22 gene reduces the expression of its encoded LYP, which increases the risk of GD and HT. GD is an organ-specific autoimmune disease involving increased secretion of thyroid hormone, whereas HT may be associated with the destruction of thyroid gland tissue and hypothyroidism. These two diseases exhibit similar pathogenesis but opposite trends in the clinical manifestations. In this review, we focus on the structure and function of these cytokines and related genes in AITD, as well as the association of polymorphisms with susceptibility to GD and HT, and attempt to describe their differences in pathogenesis and clinical manifestations.

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Human leukocyte antigen class II variants and adult-onset asthma: does occupational allergen exposure play a role?

Cited by 10 publications

References 40 publications

Allergic and Nonallergic Asthma Have Distinct Phenotypic and Genotypic Features

Allergic and Nonallergic Asthma Have Distinct Phenotypic and Genotypic Features

Genes Interacting with Occupational Exposures to Low Molecular Weight Agents and Irritants on Adult-Onset Asthma in Three European Studies

General and Specific Genetic Polymorphism of Cytokines-Related Gene in AITD

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