Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Free Radic Biol Med. 2008 Sep 1;45(5):645-50. doi: 10.1016/j.freeradbiomed.2008.05.012. Epub 2008 May 24.

Functional significance of the GAG trinucleotide-repeat polymorphism in the gene for the catalytic subunit of gamma-glutamylcysteine ligase.

Author information

  • 1Cancer Prevention and Control Program, Penn State Cancer Institute, Department of Public Health Sciences, Penn State University College of Medicine, Hershey, PA 17033, USA.

Abstract

Gamma-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.

PMID:
18549827
[PubMed - indexed for MEDLINE]
PMCID:
PMC2562218
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk