Identifying Shared Genetic Susceptibility Regions in Chronic Beryllium Disease and Sarcoidosis
Condition: Sarcoidosis; Berylliosis
MeSH terms: Berylliosis; Sarcoidosis; Genetic Predisposition to Disease
Study type: Observational

Summary: 
      Granulomatous lung diseases are diseases in which inflamed clusters of white cells, known as
      granulomas, form in lung tissue. Chronic beryllium disease (CBD) and sarcoidosis are two
      granulomatous diseases that share similar clinical symptoms, physiological changes in the
      lungs, and immune responses to the disease. Genetic variations may make some people more
      susceptible to developing CBD or sarcoidosis. This study will identify common genetic regions
      associated with increased risk of developing the granulomatous diseases CBD and sarcoidosis.
    

Detailed description: 
      CBD and sarcoidosis are granulomatous lung diseases that are caused by an abnormal immune
      response. While CBD is known to develop from exposure to the industrial product beryllium,
      the cause of sarcoidosis remains undetermined. CBD occurs in 2 to 16% of people exposed to
      beryllium and varies in severity of symptoms. People with sarcoidosis often show very minor
      symptoms. However, certain variables have been associated with the more severe forms of
      disease. These variables include black race, onset over the age of 40, involvement of more
      than three affected organs, and presence of more serious lung disease. When serious symptoms
      of sarcoidosis occur, clinical and pathological appearances of CBD and sarcoidosis are often
      hard to distinguish. Symptoms common to both diseases include fever, chest pain, weight loss,
      night sweats, fatigue, and presence of granulomas on the lungs. The fact that the severity of
      both diseases varies greatly among those affected points to possible genetic involvement. The
      genetic basis being analyzed in this study begins with the similar immune responses in the
      development of both diseases, specifically involving human leukocyte antigen (HLA) gene
      products. The purpose of this study is to identify common genetic regions associated with
      increased risk of developing the granulomatous diseases CBD and sarcoidosis.

      This study will utilize a novel technique, known as a genome-wide scan. The study will
      examine previously collected DNA samples from participants in a previous NIH study, A Case
      Control Etiologic Study of Sarcoidosis (ACCESS), and from participants with CBD recruited at
      the National Jewish Medical and Research Center. Using the genome scans, researchers will
      compare genetic regions of people with CBD versus people without CBD who have been exposed to
      beryllium. The same approach will be used to define genetic regions associated with
      sarcoidosis. Genome control methods will be used to account for population stratification in
      both the CBD and sarcoidosis populations. Researchers will compare data between diseased and
      healthy control groups and between CBD and sarcoidosis groups to identify shared genetic
      regions relevant to disease development. A second genome scan involving two larger
      populations of CBD and sarcoidosis cases and controls will be conducted to confirm the
      association of these regions with both diseases.
    

Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        This study will use specimens from two well-established disease popultions: a CBD
        population previously recruited at the National Jewish Medical and Research Center and a
        sarcoidosis population derived from the previous NHLBI study, A Case-Control Etiologic
        Study of Sarcoidosis (ACCESS).
      
Biospecimen description: 
      DNA specimens
    
Keywords: Chronic Beryllium Disease; CBD; Beryllium; Genetic; Environmental