Background: A beryllium materials manufacturer is conducting a limited pilot program that offers testing for HLA-DP beta 1E69 with genetic counseling through a third party to applicants for employment. An important consideration in this regard is the prevalence of this marker in the general population, and its consequent positive predictive value of disease susceptibility.
Methods: Polymerase chain reaction and restriction fragment length polymorphism analyses were used to determine HLA-DP beta 1E69 population frequencies. Estimation of positive predictive values assumed a disease frequency among beryllium workers of either 5 or 15% and used an odds ratio for disease risk of 35 for the HLA-DP beta 1E69 marker.
Results: Allelic/carrier frequencies were found to be 0.21/0.33, 0.24/0.40, 0.27/0.47, and 0.38/0.59 for Caucasians, African-Americans, Hispanics, and Chinese, respectively. Ranges of positive predictive values for a genetic test based on HLA-DP beta 1E69 in these populations were calculated to be 8.3-14.3% for carriers with an assumed disease frequency of 5%. For high risk subgroups with disease frequencies of 15%, the range of positive predictive values was found to span between 24.9-43.0%.
Conclusions: These estimates suggest that using HLA-DP beta 1E69 genotyping for general pre-employment screening in the beryllium industry has a low positive predictive value, which varies little among racial groups where carrier frequencies differ significantly.