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Case-Control Study of Environmental Exposures and Genetic Susceptibility in Individuals with Multiple Sclerosis in Three Geographic Areas

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Background:

Although multiple sclerosis (MS) is the most common neurologic disease disabling young adults in the United States, the cause of this disease is unknown. Evidence indicates that it is a complex disease with a multifactorial etiology determined by both environmental factors and genetic susceptibility. However, previous research examining potential causes of MS has focused on either the role of environmental exposures, or the role of genetic factors, but not a combination of the two. Therefore, we propose to extend and improve upon previous research by conducting a case-control study with a case-only component to examine the joint role of select environmental exposures and candidate genes as potential risk factors of MS. Through this effort we will address the following research questions:

  • Are exposures to heavy metals or other toxic chemicals associated with increased risk of MS?
  • Does exposure to infectious diseases increase the risk of MS?
  • Are certain candidate genes associated with an increased risk of MS?
  • Does the combination of environmental exposures and genetic susceptibility in candidate genes increase risk of MS? Gene-environment interactions to be examined include the combination of each candidate gene with exposure to heavy metals, toxic chemicals and infectious disease antibodies.
  • Is there increased risk of MS associated with gene-gene interaction (i.e. combinations of each of the candidate genes examined)?

Study Design:

This study will be conducted over a three year period and will enroll 1500 individuals (500 cases and 1000 controls). To be considered for study eligibility, cases will include individuals who have been diagnosed with MS and were identified through the prevalence studies that are currently being completed in Ohio, Missouri, and Texas by local and state health departments under a cooperative agreement with ATSDR. In each of the study areas, information on all MS cases with a patient visit during the study period of January 1, 1998 to December 31, 2000 was collected. Case status was determined by the reviewing neurologist by applying both the Poser and McDonald criteria to the clinical and laboratory data available in the patient's record. Controls will be selected from patients who attended the same neurologist's office from which the cases arose and who had a patient visit during the study period. The diagnoses for control selection will be limited to those for which there is no prior indication of a relation with the exposures under study.

In order to examine the joint role of select environmental exposures and candidate genes as potential risk factors of multiple sclerosis, we are in the process of:

  • Enrolling 500 individuals with MS who were identified through the prevalence study to serve as cases.
  • Enrolling 1000 individuals without MS who attended the same neurologists office, clinic or hospital in which cases were identified to serve as controls.
  • Obtaining information, by questionnaire, on exposure to heavy metals and other toxic chemicals either through occupational exposures, hobbies or lifestyle activities, or due to residential proximity to industry or hazardous waste sites.
  • Obtaining a blood specimen from all study participants to measure antibodies to Epstein-Barr virus which has been postulated to be a potential risk factor of disease.
  • Obtaining a blood specimen from all study participants to evaluate specific candidate genes including human leukocyte antigen, T cell antigen receptor (a and ß), myelin basic protein, tumor necrosis factor, vitamin D receptor and apolipoprotein E as potential risk factors of disease.
Last updated February 09, 2011