Endotoxin exposure,<i>CD14</i>and wheeze among farmers: a gene–environment interaction

Smit, Lidwien A M; Heederik, Dick; Doekes, Gert; Koppelman, Gerard H.; Bottema, R. W. B.; Postma, Dirkje S.; Wouters, Inge M.

doi:10.1136/oem.2010.060038

Cited by 26 publications

(34 citation statements)

References 33 publications

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“…40 Inversely, we did not observe any associations of CD14 SNPs rs2569190 and rs2569191 with sCD14 protein levels in plasma, but ex vivo stimulations of peripheral blood with LPS revealed significant differences in secreted TNF levels when comparing the AA and AG genotypes for rs2569190 and the CC genotype compared with either CT or TT for rs2569191. These apparent contradictions need to be considered in the context of differences in population demographics, age and disease context: Munthe-Kaas et al 39 showed that rs2569190 and rs2569191 were associated with serum sCD14 protein levels in Norwegian children up to 2 yrs of age, but not in those older than 2 yrs of age.…”

Section: Discussioncontrasting

confidence: 58%

Identification of single nucleotide polymorphisms in hematopoietic cell transplant patients affecting early recognition of, and response to, endotoxin

et al. 2013

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Hematopoietic cell transplant (HCT) is a life-saving therapy for many malignant and non-malignant bone marrow diseases. Associated morbidities are often due to transplant-related toxicities and infections, exacerbated by regimen-induced immune suppression and systemic incursion of bacterial products. Patients undergoing myeloablative conditioning for HCT become endotoxemic and display blood/plasma changes consistent with lipopolysaccharide (LPS)-induced systemic innate immune activation. Herein, we addressed whether patients scheduled for HCT display differences in recognition/response to LPS ex vivo traceable to specific single nucleotide polymorphisms (SNPs). Two SNPs of LPS binding protein (LBP) were associated with changes in plasma LBP levels, with one LBP SNP also associating with differences in efficiency of extraction and transfer of endotoxin to myeloid differentiation factor-2 (MD-2), a step needed for activation of TLR4. None of the examined SNPs of CD14, bactericidal/permeability-increasing protein (BPI), TLR4 or MD-2 were associated with corresponding protein plasma levels or endotoxin delivery to MD-2, but CD14 and BPI SNPs significantly associated with differences in LPS-induced TNF-α release ex vivo and infection frequency, respectively. These findings suggest that specific LBP, CD14 and BPI SNPs might be contributory assessments in studies where clinical outcome may be affected by host response to endotoxin and bacterial infection.

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Section: Discussioncontrasting

confidence: 58%

Identification of single nucleotide polymorphisms in hematopoietic cell transplant patients affecting early recognition of, and response to, endotoxin

et al. 2013

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“…There have been a limited number of studies in adults showing an association between CD14 polymorphisms and several lung phenotypes such as asthma and allergy [39, 40], wheeze [41], pulmonary tuberculosis [42] and pulmonary function [41, 43–45]. While the results of the present study show a weak association between CD14 polymorphisms and lung function, we found a significant interaction between CD14 haplotypes and sCD14 levels on lung function.…”

Section: Discussioncontrasting

confidence: 75%

“…Many multiplicative interactions have been found with CD14 polymorphisms and environmental exposures. In a study of Dutch farmers and agriculture industry workers, increased environmental exposure to endotoxin in those with the CD14 /-1720 T or CD14 /-260G allele was associated with lower FEV 1 values compared to those homozygous for the C or A allele [41]. In contrast, in a study of laboratory animal workers, those with high endotoxin exposure and the CD14 /-1720C allele had significantly lower lung function than workers with the TT genotype [43].…”

Section: Discussionmentioning

confidence: 99%

Interaction of CD14 haplotypes and soluble CD14 on pulmonary function in agricultural workers

et al. 2017

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BackgroundAgricultural environments are contaminated with organic dusts containing bacterial components. Chronic inhalation of organic dusts is implicated in respiratory diseases. CD14 is a critical receptor for gram-negative lipopolysaccharide; however, its association with respiratory disease among agricultural workers is unknown. The objective of this study was to determine if serum soluble CD14 (sCD14) levels are associated with lung function among agricultural workers and if this association is modified by genetic variants in CD14.MethodsThis cross-sectional study included 584 veterans with >2 years of farming experience and that were between the ages of 40 and 80 years. Participants underwent spirometry and were genotyped for four tagging CD14 polymorphisms (CD14/-2838, rs2569193; CD14/-1720, rs2915863; CD14/-651, rs5744455; and CD14/-260, rs2569190). Serum sCD14 was assayed by ELISA.ResultsSubjects were 98% white males with a mean age 64.5 years. High soluble CD14 levels (> median sCD14) were associated decreased lung function (FEV1/FVC, p = 0.011; % predicted FEV1, p = 0.03). When stratified by COPD (yes/no) and smoking status (ever/never), high sCD14 levels (> median sCD14) were associated with low lung function among ever smokers with COPD (% predicted FEV1, padj = 0.0008; FEV1/FVC, padj = 0.0002). A similar trend was observed for never smokers with COPD; however, results did not reach statistical significance due to small sample size. There was a significant sCD14 x COPD/smoking interaction with lung function (% predicted FEV1, pinter = 0.0498; FEV1/FVC, pinter = 0.011). Regression models were adjusted for age, body mass index, education, sex, race and years worked on a farm. No association was found between CD14 polymorphisms/haplotypes (CD14/-2838; CD14/-1720; CD14/-651; CD14/-260) and sCD14 levels. The final model included the variables sCD14 and haplotypes and a haplotype x sCD14 interaction term. Individuals with the GTTG haplotype (CD14/-2838 → CD14/-260) and high sCD14 levels (> median sCD14) had on average 6.94 lower % predicted FEV1 than individuals with the GCCA haplotype and low sCD14 levels (≤ median sCD14, padj = 0.03).Conclusion CD14 haplotypes and sCD14 are important mediators of lung function among those with COPD in this occupationally-exposed population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-017-0532-y) contains supplementary material, which is available to authorized users.

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“…It has been argued that interactions between genetic factors and the environment is of importance and more polymorphisms in genes crucial in the innate immune system (i.e., TLR4, CD14 and MD2) have been associated with endotoxin responsiveness. [52][53][54] A recently published study among children, however, did not support common polymorphisms to be important for the observed protective effect of early farming exposure. 55 Besides sensitization and allergic asthma, a similar protective effect of endotoxin exposure has been proposed for lung cancer.…”

Section: Respiratory Health Effectsmentioning

confidence: 98%

A comprehensive review of levels and determinants of personal exposure to dust and endotoxin in livestock farming

Basinas

Sigsgaard

Kromhout

et al. 2013

J Expo Sci Environ Epidemiol

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The respiratory health effects of livestock farming have been on debate for more than three decades. Endotoxin-contaminated organic dusts are considered as the most important respiratory hazards within livestock environments. A comprehensive review of the knowledge from studies assessing the exposure status of livestock farmers is still to be published. The present study reviews research published within the last 30 years on personal exposure of livestock farmers to organic dust and endotoxin, focusing on studies on pig, poultry and cattle farmers. Applied measurement methods and reported levels of personal exposure for the total, inhalable and respirable fractions are summarized and discussed, with emphasis on the intensity of exposure and the size and distribution of the reported exposure variability. In addition, available evidence on potential determinants of personal exposure to dust and endotoxin among these farmers are documented and discussed, taking results from exposure determinant studies using stationary sampling approaches into consideration. Research needs are addressed from an epidemiological and industrial hygiene perspective. Published studies have been heterogeneous in design, and applied methodologies and results were frequently inadequately reported. Despite these limitations and the presence of an enormous variability in personal exposure to dust and endotoxin, no clear downward trends in exposure with time were observed, suggesting that working environments within stables remains largely uncontrolled. Exposure control and prevention strategies for livestock farmers are urgently required. These should focus on the development of novel and improved methods of controlling dust and endotoxin exposure within stables based on the currently available knowledge on determinants of exposure.

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Endotoxin exposure,CD14and wheeze among farmers: a gene–environment interaction

Cited by 26 publications

References 33 publications

Identification of single nucleotide polymorphisms in hematopoietic cell transplant patients affecting early recognition of, and response to, endotoxin

Identification of single nucleotide polymorphisms in hematopoietic cell transplant patients affecting early recognition of, and response to, endotoxin

Interaction of CD14 haplotypes and soluble CD14 on pulmonary function in agricultural workers

A comprehensive review of levels and determinants of personal exposure to dust and endotoxin in livestock farming

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