Online Program

333429
Relationships between TLR4 pathway Single Nucleotide Polymorphisms, Distance to Roadway, and Asthma Diagnosis and Severity


Wednesday, November 4, 2015 : 11:10 a.m. - 11:30 a.m.

Mercedes Bravo, Ph.D., Children's Environmental Health Initiative, School of Natural Resources and Environment, University of Michigan, Ann Arbor, MI
Shepherd Schurman, M.D., Clinical Research Unit, National Institute of Environmental Health Sciences, Research Triangle Park, NC
Stavros Garantziotis, MD, National Institute of Environmental Health Sciences, Research Triangle Park, NC
Ben Strauss, MS, Children's Environmental Health Initiative, Durham, NC
Marie Lynn Miranda, PhD, School of Natural Resources & Environment, University of Michigan, Ann Arbor, MI
Asthma is a complex chronic health condition estimated to affect 25 million people in the United States alone. Gene by environment interactions may play a role in determining asthma incidence or severity. Previous work indicates that specific gene polymorphisms on the TLR4 pathway are associated with asthma incidence.  We examine four common single nucleotide polymorphisms (SNPs) that have functional effects on TLR4 signaling: two gain-of-function SNPs, CD14 and TNFa; and two loss-of-function SNPs, TLR4 and TIRAP.  Our objective was to explore possible gene-environment interactions by examining SNP combinations, residential distance to roadway as a proxy for traffic-related air pollution exposure, and asthma outcomes.

We obtained individual-level data from the Environmental Polymorphisms Registry, including SNP data, residential address, and asthma diagnosis and symptoms. Subjects (n=1,823) were divided into three “responder type” groups based on genetic profiles: (1) hyper-responders (carriers of CD14 and TNFa and wild-type TLR4 and TIRAP); (2) hypo-responders (carriers of TLR4 and/or TIRAP and wild-type CD14 and TNFa); and (3) others. We geocoded addresses and calculated the distance between each subject’s residence and nearest road, considering highways, major roads, and secondary/connecting roads. We classified each subject’s proximity to the nearest road as either <250m or >250m; in a sensitivity analysis, we used this distance classification but only considered proximity to highways and major roads (i.e., excluding secondary/connecting roads). Asthma outcomes were examined separately using a logistic regression model (asthma diagnosis) and cumulative logit model (asthma-related sleeplessness, activity limitations, emergency room [ER] visits). Covariates included sex, smoking status, race, and home environmental tobacco smoke.

Over half of the subjects (n=1,016, 55.7%) lived >250m from the nearest road; 807 subjects (44.3%) lived <250m from the nearest road. Whites were more likely than blacks/African Americans to report asthma diagnosis (OR=1.33, CI: 1.07, 1.65), and men were less likely to report asthma diagnosis (OR=0.53, CI: 0.43, 0.64) and symptoms. Individuals closer to roads (<250m) were more likely to report asthma diagnosis (OR=1.25, CI: 1.03, 1.52).  Hypo responders were less likely than hyper responders to report asthma-related activity limitations (OR=0.58, CI: 0.36, 0.98).  Sensitivity analysis results were consistent with the main analysis findings; additionally, for subjects <250 from a road, regular responders were less likely than hyper responders to report more severe asthma, as indicated by asthma-related ER visits (OR=0.37, CI: 0.14, 0.97).

Learning Areas:

Chronic disease management and prevention
Environmental health sciences
Epidemiology

Learning Objectives:
Evaluate possible gene-environment interactions in asthma incidence and severity by examining SNP combinations, residential distance to roadway as a proxy for traffic-related air pollution exposure, and asthma outcomes

Keyword(s): Asthma, Genetics

Presenting author's disclosure statement:

Qualified on the content I am responsible for because: I received my Ph.D. in Environmental Epidemiology in 2014 and have completed coursework on epidemiology, statistical analysis, and study design. Further, I have published in peer reviewed journals on these topics. My co-authors on this analysis and presentation are experienced researchers and physicians.
Any relevant financial relationships? No

I agree to comply with the American Public Health Association Conflict of Interest and Commercial Support Guidelines, and to disclose to the participants any off-label or experimental uses of a commercial product or service discussed in my presentation.