.2018 Aug 23;8(1):12713.

doi: 10.1038/s41598-018-30865-0.

Toll-like Receptor 4 Pathway Polymorphisms Interact with Pollution to Influence Asthma Diagnosis and Severity

Shepherd H Schurman¹, Mercedes A Bravo², Cynthia L Innes¹, W Braxton Jackson 2nd³, John A McGrath³, Marie Lynn Miranda^{4 5}, Stavros Garantziotis⁶

Affiliations

¹ Clinical Research Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, 27709, United States.
² Children's Environmental Health Initiative, Rice University, Houston, Texas, 77005, United States.
³ Social and Scientific Systems, Durham, North Carolina, 27703, United States.
⁴ Children's Environmental Health Initiative, Rice University, Houston, Texas, 77005, United States. mlm@rice.edu.
⁵ Department of Statistics, Rice University, Houston, Texas, 77005, United States. mlm@rice.edu.
⁶ Clinical Research Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, 27709, United States. garantziotis@niehs.nih.gov.

PMID:30140039
PMCID: PMC6107668
DOI: 10.1038/s41598-018-30865-0

Toll-like Receptor 4 Pathway Polymorphisms Interact with Pollution to Influence Asthma Diagnosis and Severity

Shepherd H Schurman et al. Sci Rep.2018.

.2018 Aug 23;8(1):12713.

doi: 10.1038/s41598-018-30865-0.

Authors

Shepherd H Schurman¹, Mercedes A Bravo², Cynthia L Innes¹, W Braxton Jackson 2nd³, John A McGrath³, Marie Lynn Miranda^{4 5}, Stavros Garantziotis⁶

Affiliations

¹ Clinical Research Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, 27709, United States.
² Children's Environmental Health Initiative, Rice University, Houston, Texas, 77005, United States.
³ Social and Scientific Systems, Durham, North Carolina, 27703, United States.
⁴ Children's Environmental Health Initiative, Rice University, Houston, Texas, 77005, United States. mlm@rice.edu.
⁵ Department of Statistics, Rice University, Houston, Texas, 77005, United States. mlm@rice.edu.
⁶ Clinical Research Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, 27709, United States. garantziotis@niehs.nih.gov.

PMID:30140039
PMCID: PMC6107668
DOI: 10.1038/s41598-018-30865-0

Abstract

Asthma is a common chronic lung disease, the incidence and severity of which may be influenced by gene-environment interactions. Our objective was to examine associations between single nucleotide polymorphisms (SNPs) and combinations of SNPs in the toll-like receptor 4 (TLR4) pathway, residential distance to roadway as a proxy for traffic-related air pollution exposure, and asthma diagnosis and exacerbations. We obtained individual-level data on genotype, residential address, and asthma diagnosis and exacerbations from the Environmental Polymorphisms Registry. Subjects (n = 2,704) were divided into three groups (hyper-responders, hypo-responders, and neither) based on SNP combinations in genes along the TLR4 pathway. We geocoded subjects and calculated distance, classified as <250 m or ≥250 m, between residence and nearest major road. Relationships between genotype, distance to road, and odds of asthma diagnosis and exacerbations were examined using logistic regression. Odds of an asthma diagnosis among hyper-responders <250 m from a major road was 2.37(0.97, 6.01) compared to the reference group (p < 0.10). Hypo-responders ≥250 m from the nearest road had lower odds of activity limitations (0.46 [0.21, 0.95]) and sleeplessness (0.36 [0.12, 0.91]) compared to neither-responders (p < 0.05). Specific genotype combinations when combined with an individual's proximity to roadways, possibly due to traffic-related air pollution exposure, may affect the likelihood of asthma diagnosis and exacerbations.

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Conflict of interest statement

The authors declare no competing interests.

Figures

**Figure 1**
Genotyped EPR Cohort Distribution based on Residential Address, North Carolina.

See this image and copyright information in PMC

References

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Toll-like Receptor 4 Pathway Polymorphisms Interact with Pollution to Influence Asthma Diagnosis and Severity

Affiliations

Toll-like Receptor 4 Pathway Polymorphisms Interact with Pollution to Influence Asthma Diagnosis and Severity

Authors

Affiliations

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Conflict of interest statement

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References

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