Official websites use. Share sensitive information only on official, secure websites. Corresponding author: Address correspondence to: John P. Richie, Jr. In a subset of individuals, blood GCL activity was determined. Five alleles with 4, 7, 8, 9 and 10 GAG repeats were observed.
Such individuals might be more susceptible to oxidative stress-related diseases than individuals with other genotypes. These functions include detoxifying drugs [ 1 ], protecting macromolecules from reactive oxygen species [ 2 ] and modulating protein structure and function [ 3 ].
More recently, GSH has been found to play important roles in signal transduction [ 4 ], cell proliferation [ 5 ], apoptosis [ 6 ] and gene expression [ 7 ]. Based upon these many functions, maintenance of optimal GSH concentration in cells and tissues represents a critical factor in the maintenance of health and susceptibility to diseases. Decreased GSH levels have been implicated in numerous diseases such as heart disease [ 8 ], arthritis [ 8 , 9 ], diabetes [ 8 , 9 ] and cancers [ 10 - 12 ].
While large interindividual variation in GSH levels has been observed [ 13 , 14 ], little is known about the intrinsic and extrinsic factors responsible for this variation, particularly as it relates to disease risk or treatment toxicities involving GSH depletion. Two enzymes are responsible for the biosynthesis of GSH in cells and tissues. Glutathione synthetase EC 6. It has been observed that the distribution of the allele with the 4 GAG-repeat is restricted to blacks and the 10 GAG-repeat allele restricted to blacks and Hispanics [ 18 ].
This polymorphism has been associated with several disease conditions such as schizophrenia [ 19 ], chronic beryllium disease [ 20 ] and diabetes [ 21 ]. However, the in vivo functional significance of the GAG polymorphism on GSH biosynthesis has not been previously examined.
