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 (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.
Bekris
Lynn M
LM
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington 98195, USA.
Viernes
Hannah-Malia A
HM
Farin
Federico M
FM
Maier
Lisa A
LA
Kavanagh
Terrance J
TJ
Takaro
Tim K
TK
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
D005721:Glutamate-Cysteine Ligase; D005978:Glutathione