Chronic beryllium disease and glutathione biosynthesis genes

J Occup Environ Med. 2006 Jun;48(6):599-606. doi: 10.1097/


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 (GCLM).

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 (SNP), and the GCLM-588 SNP.

Results: 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.

Conclusions: This study suggests that GSH modulation may play a role in CBD pathogenesis, but not in sensitization to beryllium.

Publication types

  • Research Support, N.I.H., Extramural

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


  • Glutamate-Cysteine Ligase
  • Glutathione