Autor/a:
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Rava, Marta; Ahmed, Ismail; Kogevinas, Manolis; Le Moual, Nicole; Bouzigon, Emmanuelle; Curjuric, Ivan; Dizier, Marie-Hélène; Dumas, Orianne; González, Juan Ramón; Imboden, Medea; Mehta, Amar J.; Tubert-Bitter, Pascale; Zock, Jan-Paul; Jarvis, Deborah; Probst-Hensch, Nicole M.; Demenais, Florence; Nadif, Rachel
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Abstract:
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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 (GxE) may help identify new genes
related to adult-onset asthma. OBJECTIVES: To identify
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: Data came from three
large European cohorts: EGEA, SAPALDIA, and ECRHS. A candidate
pathway-based strategy identified 163 genes involved in response
to oxidative stress and potentially related with 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 GxE interactions, adjusted
for age, sex and population ancestry in 2599 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(95%CI)=1.28(1.04,1.58)). Eight 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 the adult asthma in relation with
occupational exposure. These genes play a role in the NF-kB
pathway involved in inflammation. |