Chronic beryllium disease and glutathione biosynthesis genes

Objective: Because glutathione (GSH) has been reported to be increased in chronic beryllium disease (CBD) and is associated With immune modulation, associations between CBD and gene polymorphisms of the rate-limiting enzyme in GSH synthesis, glutamate cysteine ligase (GCL), were investigated. Glutamate cysteine ligase consists of a catalytic subunit (GCLC) and modifier subunit (GCLAM). Methods: Patients with CBD, beryllium-sensitized subjects (BeS), and beryllium-exposed subjects without CBD were genotyped for the GCLC GAG trinucleotide repeat polymorphism (GCLC TNR), the GCLC-129 single nucleotide polymorphism (SAP), and the GCLM-588 SAP. Results: Results indicate that GCLC TNR genotype 717 is negatively associated with CBD (odds ratio [OR] = 0.28, 95% confidence interval [CI] = 0.08-0.95) and the GCLM-588 C/C SNP genotype is associated with CBD susceptibility (OR = 3.07, 95% CI = 1.00-9.37). No differences were noted in the BeS group. Conclusions: This study suggests that GSH modulation may play a role in CBD pathogenesis, but not in sensitization to beryllium.