Polymorphism of FCGR3A gene in chronic beryllium disease
Bing Liu1, Lisa A Maier1,2,3, Nabeel Hamzeh1,2
1Division of Environmental and Occupational Health Sciences, Department of Medicine, National Jewish Health, Denver, CO, USA.
Abstract:
Previously we showed that alveolar macrophages (AMs) from patients with chronic beryllium disease (CBD) and beryllium sensitization (BeS) demonstrated significantly greater cell surface CD16 (encoded by the FCGR3A gene) than controls. We hypothesized that these differences were related to polymorphisms in the FCGR3A gene. This study was to determine the association between FCGR3A polymorphisms in CBD, BeS versus controls as well as clinical data, providing potential information about disease pathogenesis, risk, and activity. A total of 189 CBD/154 BeS/150 controls (92 Be-exposed non-diseased and 58 healthy controls) were included in this study. Sequence-specific primers polymerase chain reaction (PCR-SSP) was used to determine FCGR3A 158V/F polymorphisms. We found significantly higher frequencies of the 158V allele (OR: 1.60 (CI: 1.17-2.19), p = 0.004) and 158VV homozygotes (OR: 2.97 (CI: 1.48-5.97) p = 0.007) in CBD versus controls. No differences were found in the frequencies of FCGR3A alleles or genotypes between BeS versus controls and CBD versus BeS. Average changes in exercise testing maximum workload (Wlm), maximum oxygen consumption (VO2m), and diffusion capacity of carbon monoxide (DLCO) demonstrated greater decline over time in those CBD cases with the 158VV gene, modeled between 10 and 40 years from first beryllium exposure. The FCGR3A V158F polymorphism is associated with CBD compared to BeS and controls and may impact lung function in CBD.
Insights
The FCGR3A V158F gene variant is linked to chronic beryllium disease (CBD), not beryllium sensitization (BeS). This polymorphism may also affect lung function decline in CBD patients.
Area of Science:
- Immunogenetics
- Pulmonary Medicine
- Occupational Health
Background:
- Alveolar macrophages (AMs) in chronic beryllium disease (CBD) and beryllium sensitization (BeS) patients show increased CD16 expression.
- CD16 is encoded by the FCGR3A gene, suggesting a potential role for its polymorphisms in CBD pathogenesis.
Purpose of the Study:
- To investigate the association between FCGR3A gene polymorphisms and CBD/BeS.
- To explore the relationship between FCGR3A polymorphisms and clinical parameters in CBD.
Main Methods:
- Genotyping of FCGR3A 158V/F polymorphisms using sequence-specific primers polymerase chain reaction (PCR-SSP).
- Analysis of 189 CBD patients, 154 BeS patients, and 150 controls (92 beryllium-exposed non-diseased, 58 healthy).
Main Results:
- Significantly higher frequencies of the 158V allele and 158VV genotype were observed in CBD patients compared to controls.
- No significant differences in FCGR3A allele or genotype frequencies were found between BeS and controls, or between CBD and BeS.
- CBD cases with the 158VV genotype showed a greater decline in exercise testing parameters (Wlm, VO2m) and DLCO over time.
Conclusions:
- The FCGR3A V158F polymorphism is associated with CBD, distinguishing it from BeS and controls.
- This genetic variation may influence the progression of lung function impairment in CBD patients.
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