The Environmental Genome Project (EGP) has completely or partially resequenced the protein coding and regulatory regions of 53 environmentally sensitive genes from 72 anonymous individuals of varying ethnic backgrounds to date. Some of the same genes have been resequenced in an additional set of 20 samples, and, in a subset of these, the introns and promoter regions have been sequenced as well. Within this population, 523 allelic variants (genetic polymorphisms), mostly single nucleotide polymorphisms (SNPs), have been found to date. If the polymorphism alters the behavior or expression of the encoded protein, it might be of clinical significance.

The Program in Clinical Research is planning to establish a large resource bank of frozen DNA samples (n=20,000) and make this available to NIEHS intramural investigators, their collaborators at the University of North Carolina (UNC), Duke University and other research institutions to screen for the presence of these SNPs and other mutations by standard genotyping methods. To investigate the feasibility of such a large DNA sample collection, we recently completed a small pilot study consisting of approximately 481 samples from patients at two UNC outpatient clinics, the Family Practice Clinic (FPC) and the Ambulatory Care Center (ACC). The major goal of this pilot study was to assess the willingness of general outpatients to participate in a genetic study of this sort and identify potential problems that might arise when conducting the larger, 20,000 sample effort. In the pilot study, recruitment procedures worked well and accrual rates were high at both sites. Of all the patients asked to participate, 75.6% and 78.1% of the patients from the FPC and ACC, respectively, agreed to participate as evidenced by signing an informed consent form. Only two patients from the FPC withdrew from the study at a later date. Based on the excellent results of the pilot study, we have therefore decided to proceed with the larger, 20,000 sample collection, which is the focus of this protocol.

Similar to the pilot study, for the larger study blood left over from patients already having their blood drawn for specific tests requiring EDTA-anticoagulated blood or purple top tube (complete blood count or CBC, sedimentation rate and hemoglobin A1c or HbA1c) as part of their routine clinical management will be asked to donate their left over blood from these tests. We will also ask other patients already having their blood drawn for other tests that do not require a purple top tube, if they will have an extra tube of blood drawn (3.0 ml purple top) just for this registry. This will eliminate having a needle stick done just for this study in the UNC Healthcare participants. In addition we plan to recruit EPR participants from other sources such as volunteer drives at various corporations throughout the RTP and other areas in NC, at the UNC and Duke campuses and the Medical Centers at both campuses, and from our EPR website. Once the samples have been obtained, the blood will be transferred into storage tubes that are identifiable only with a unique identification number and shipped to an NIEHS contractor for DNA isolation.

During recruitment, interviewers will explain the study to potential participants, obtain their signatures on the informed consent documents, and answer any questions they might have concerning this study. At this time, potential participants will be informed that, depending on the results of the genetic analyses of their blood samples, they may be recontacted at a later date and asked to participate in follow-up genotype/phenotype studies. These follow-up studies will be separate from this protocol and require their own IRB approval. The ultimate objective of these sample collections, combined with the follow-up genotype/phenotype studies, is to identify groups of individuals with genetic polymorphisms in environmentally sensitive genes, and to correlate their genotype with their clinical phenotype, a process known as ascertainment by genotype .