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Evaluation of a supratypic HLA-genetic marker for susceptibility to chronic beryllium disease: racial variation has no significant impact for pre-employment screening.

Authors
Weston-A; Ensey-J; Kreiss-K; Keshava-C; McCanlies-E
Source
Am J Hum Genet 2001 Oct; 69(4)(Suppl):444
NIOSHTIC No.
20021483
Abstract
Codon 69 of HLA-DPB1 is tri-allelic (AAG - lysine [K], GAG - glutamic acid [E] and AGG - arginine [R]), where the relative frequencies are K>E>R. The lysine allele is found in 54 of 88 known variants of this gene, glutamic acid is found in 29 and arginine in 5. Three published studies report an association of the supratypic marker HLA-DPB1E69 with susceptibility to disease following occupational exposure to beryllium, where odds ratios range between 12 and 76 (95%CIs range = 2-322). Consequently, testing for HLA-DPB1E69 is currently being considered as a pre-employment screening tool. This study investigates the prudence of this course of action in light of calculations of the positive predictive value, sensitivity and specificity of this supratypic marker in four racial populations. Polymerase chain reaction and restriction analyses were used to determine HLA-DPB1E69 population frequencies. Calculation of positive predictive values assumed a disease frequency among beryllium workers of 5% for the workforce in general. Selection of an odds ratio for disease risk of 35 for the HLA marker was based on analysis of data previously reported in the literature by others. 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, Latinas and Chinese respectively. Ranges of positive predictive values for a genetic test based on HLA-DPB1E69 in these populations were calculated to be 8.3 - 14.3% for carriers with an assumed disease prevalence of 5%. These estimates suggest that using HLA-DPB1E69 genotyping for general pre-employment screening in the beryllium industry has a low positive predictive value, regardless of the fact that there are significant differences in carrier frequencies among racial groups.
Keywords
Beryllium-disease; Racial-factors; Preemployment-examinations; Occupational-exposure; Diseases; Genetics; Genetic-factors; Screening-methods; Preemployment-examinations
CODEN
AJHGAG
CAS No.
7440-41-7
Publication Date
20011001
Document Type
Abstract; Conference/Symposia Proceedings
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Issue of Publication
4
ISSN
0002-9297
NIOSH Division
HELD
Source Name
American Journal of Human Genetics
State
WV
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