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• W2094631812 abstract "γ-Glutamylcysteine ligase (GCL) is the rate-limiting enzyme in glutathione (GSH) synthesis. A GAG-repeat polymorphism in the 5′ UTR of the gene coding for the catalytic subunit of GCL (GCLC) has been associated with altered GSH levels in vitro. Thus, we hypothesized that this polymorphism is associated with altered GCL activity and blood GSH levels in vivo. A total of 256 healthy United States black and white adults were genotyped for the GAG polymorphism and blood GSH levels were measured. In a subset of 107 individuals, blood GCL activity was determined. Five alleles with 4, 7, 8, 9, and 10 GAG repeats were observed. The most prevalent genotype was 7/9 (40%) followed by 7/7 (32%) and 9/9 (11%). GSH levels were 15% lower in 9/9 individuals than 7/9 individuals (P = 0.05). GCL activity was 21% lower in 9/9 individuals than 7/7 individuals (P = 0.04). A decreasing trend of GCL activity was observed in the order of 7/7 > 7/9 > 9/9 (P = 0.04). These findings show that 9/9 individuals have lower blood GSH levels, which is likely due to a decrease in GCL activity. Such individuals might be more susceptible to oxidative stress-related diseases than individuals with other genotypes." @default.
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• W2094631812 date "2008-09-01" @default.
• W2094631812 modified "2023-09-24" @default.
• W2094631812 title "Functional significance of the GAG trinucleotide-repeat polymorphism in the gene for the catalytic subunit of γ-glutamylcysteine ligase" @default.
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• W2094631812 doi "https://doi.org/10.1016/j.freeradbiomed.2008.05.012" @default.
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