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Genetic susceptibility to beryllium: a case–referent study of men and women of working age with sarcoidosis or other chronic lung disease
  1. Nicola Cherry1,
  2. Jeremy Beach2,
  3. Igor Burstyn3,
  4. Jillian Parboosingh4,5,
  5. Janine Schouchen2,
  6. Ambikaipakan Senthilselvan6,
  7. Larry Svenson7,
  8. Jan Tamminga5,
  9. Niko Yiannakoulias8
  1. 1Department of Medicine, University of Alberta, Edmonton, Canada
  2. 2Department of Occupational Medicine, University of Alberta, Edmonton, Canada
  3. 3Department of Environmental and Occupational Health, Drexel University, Philadelphia, Pennsylvania, USA
  4. 4Department of Medical Genetics, University of Calgary, Calgary, Canada
  5. 5ACH Molecular Diagnostic Laboratory, Alberta Health Services, Calgary, Canada
  6. 6School of Public Health, University of Alberta, Edmonton, Canada
  7. 7Surveillance and Assessment, Alberta Ministry of Health, Edmonton, Canada
  8. 8School of Geography and Earth Sciences, McMaster, Hamilton, Canada
  1. Correspondence to Dr Nicola Cherry, Division of Preventive Medicine, University of Alberta, 5-22 University Terrace, 8303-112St, Edmonton, Alberta, Canada T6G 2T4; Nicola.cherry{at}


Objective The study was designed to investigate whether beryllium exposure was related to illness diagnosed as sarcoidosis. Chronic beryllium disease (CBD) and sarcoidosis are clinically and pathologically indistinguishable, with only the presence of beryllium-specific T-lymphocytes identifying CBD. Testing for such cells is not feasible in community studies of sarcoidosis but a second characteristic of CBD, its much greater incidence in those with a glutamic acid residue at position 69 of the HLA-DPB1 gene (Glu69), provides an alternative approach to answering this question.

Methods Cases of sarcoidosis aged 18–60 years diagnosed in Alberta, Canada, from 1999 to 2005 were approached through their specialist physician, together with age-matched and sex-matched referents with other chronic lung disease. Referents were grouped into chronic obstructive pulmonary disease (COPD), asthma and other lung disease. Participants completed a telephone questionnaire, including industry-specific questionnaires. DNA was extracted from mailed-in mouthwash samples and genotyped for Glu69. Duration of employment in types of work with independently documented beryllium exposure was calculated.

Results DNA was extracted for 655 cases (270 Glu69 positive) and 1382 referents (561 positive). No increase in sarcoidosis was seen with either Glu69 or beryllium exposure (none, <10, ≥10 years) as main effects: longer duration in possible beryllium jobs was related to COPD. In Glu69 positive men with exposure ≥10 years, the trend towards increasing rate of COPD was reversed, and a significant interaction of duration of exposure and Glu69 was detected (OR=4.51 95% CI 1.17 to 17.48).

Conclusions The gene–environment interaction supports the hypothesis that some cases diagnosed as sarcoidosis result from occupational beryllium exposure.

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