Title: Chronic beryllium disease and glutathione biosynthesis genes.

Authors: Bekris, Lynn M; Viernes, Hannah-Malia A; Farin, Federico M; Maier, Lisa A; Kavanagh, Terrance J; Takaro, Tim K

Published In J Occup Environ Med, (2006 Jun)

Abstract: 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 (GCLM).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 (SNP), and the GCLM-588 SNP.Results indicate that GCLC TNR genotype 7/7 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.This study suggests that GSH modulation may play a role in CBD pathogenesis, but not in sensitization to beryllium.

PubMed ID: 16766924

MeSH Terms: Aged; Aged, 80 and over; Berylliosis/genetics*; Catalytic Domain; Chronic Disease; Female; Genetic Predisposition to Disease; Genotype; Glutamate-Cysteine Ligase/genetics*; Glutathione/biosynthesis*; Humans; Male; Middle Aged; Polymorphism, Genetic*; Polymorphism, Single Nucleotide