title: Chronic beryllium disease and glutathione biosynthesis genes.
abstract: 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.
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Bekris
authors.forename: Hannah-Malia A
authors.initials: HM
authors.lastname: Viernes
authors.forename: Federico M
authors.initials: FM
authors.lastname: Farin
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Maier
authors.forename: Terrance J
authors.initials: TJ
authors.lastname: Kavanagh
authors.forename: Tim K
authors.initials: TK
authors.lastname: Takaro
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001607:Berylliosis / Q000235:genetics*; D020134:Catalytic Domain; D002908:Chronic Disease; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005721:Glutamate-Cysteine Ligase / Q000235:genetics*; D005978:Glutathione / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide
chemical_list: D005721:Glutamate-Cysteine Ligase; D005978:Glutathione