The Environmental Polymorphism Registry: A Unique Resource that Facilitates Translational Research of Environmental Disease

Abstract

Background: Dissecting complex disease has become more feasible because of the availability of large-scale DNA resources and advances in high-throughput genomic technology. Although these tools help scientists identify potential susceptibility loci, subjects with relevant genotypes are needed for clinical phenotyping and toxicity studies.Objective: We have developed a resource of subjects and their DNA to use for translational research of environmental disease.Methods: More than 15,000 individuals of diverse sex, age, race, and ethnicity were recruited from North Carolina. DNA was isolated from their blood and coded with personal identification numbers linked to their identities. This linked resource of subjects and their DNA—the Environmental Polymorphism Registry (EPR)—allows scientists to screen for individuals with genotypes of interest and invite them to participate in follow-up studies.Discussion: The EPR is a phenotype-by-genotype resource designed to facilitate translational studies of environmental disease. Based on their genotypes, subjects are invited to participate at all levels of research, from basic laboratory ex vivo cell phenotyping experiments that require viable tissue to in vivo observational studies and clinical trials. Here we report on progress of the EPR since 2008. We also describe a major effort at the National Institute of Environmental Health Sciences (NIEHS) to investigate susceptibility loci in 87 environmental response genes and gene × environment interactions using EPR resources.Conclusion: The EPR is a unique and novel resource and is ideal for genotype-driven translational research of environmental disease. We expect that it will serve as a model for future resources. Such tools help scientists attain their ultimate goals: to identify at-risk populations and develop strategies for preventing and treating human disease.

APOε4 is associated with enhanced in vivo innate immune responses in human subjects

“…Normal, healthy subjects were identified by APOE genotype using the NIEHS Environmental Polymorphisms Registry, 11 and enrolled in accordance with an NIEHS IRB-approved protocol. Exclusion criteria included age<18 years, active smoking, use of anti-inflammatory (e.g., non-steroidal anti-inflammatory drugs) or immunosuppressive (e.g., corticosteroids) agents, confirmed/suspected immunodeficiency, and recent gastrointestinal or respiratory illness.…”

TLR5 participates in the TLR4 receptor complex and biases towards MyD88-dependent signaling in environmental lung injury

“…We hypothesized that carriers of this SNP may have reduced TLR4-mediated inflammation. We used the Environmental Polymorphisms Registry (35), a NIEHS-supported cohort, to recruit carriers of this allele, as well as “wildtype” controls. Others have reported that whole blood from rs5744168 minor-allele carriers does not differ in the response to LPS compared to “wildtype” (31), and we confirmed this finding ( Supplemental Figure 3A ).…”

p53-responsive TLR8 SNP enhances human innate immune response to respiratory syncytial virus

“…Thirty healthy subjects (24-69 years) were recruited from the EPR under the approved National Institute of Environmental Health Sciences (NIEHS) Institutional Review Board Protocol 04-E-0053. The EPR is a long-term project to facilitate genotype-driven research and translational studies of environmental diseases (15). DNA samples have been collected and stored from over 15,000 volunteers from a racially diverse population including many in the greater North Carolina Triangle Region, USA (15).…”

“…The EPR is a long-term project to facilitate genotype-driven research and translational studies of environmental diseases (15). DNA samples have been collected and stored from over 15,000 volunteers from a racially diverse population including many in the greater North Carolina Triangle Region, USA (15). Each subject signed an informed consent form after a thorough explanation of the study.…”

“…Polymorphisms Registry (EPR). The EPR is a resource established to facilitate genotype-driven research and translational studies of environmental diseases (15). DNA samples have been collected and stored from over 15,000 mostly North Carolinian volunteers of diverse sex, age, race, and ethnicity.…”