Authors: Agúúndez, Joséé AG; Ladero, Joséé M

Source: Pharmacogenomics, Volume 9, Number 3, March 2008 , pp. 359-363(5)

Publisher: Future Medicine

Abstract:

<bold>Moyer AM, Salavaggione OE, Hebbring SJ et al.: Glutathione S-transferase T1 and M1: gene sequence variation and functional genomics. Clin. Cancer Res. 13, 7207--7216 (2007).</bold> Genetic variations in the glutathione S-transferases GSTT1 and GSTM1 have been studied in many human populations, and association of these variations with environmentally-related cancers, drug-induced hepatotoxicity and even chronification of viral hepatitis has been shown. However, studies carried out to date have been limited to gene deletion, designated as null alleles, and no extensive studies on other types of genetic variations have been carried out. This study is of great importance, as it describes the occurrence and the allele frequencies for 18 SNPs in the GSTT1 gene, including four nonsynonymous SNPs, and 69 SNPs, two of which are nonsynonymous, in the GSTM1 gene. The GSTT1 SNPs leading to the amino acid substitutions Asp43Asn, Thr65Met, Thr104Pro and a single nucleotide deletion in exon 4 cause a decrease in immunoreactive protein. Interestingly, the previously described nonsynonymous GSTT1 SNPs rs2266635 (Ala21Thr), rs11550606 (Leu30Pro), rs17856199 (Phe45Cys), rs11550605 (Thr104Pro), rs2266633 (Asp141Asn) and rs2234953 (Glu173Lys) were not identified in 400 subjects, thus indicating that these variant alleles are expected to occur at extremely low frequencies. This study reinforces the need to combine SNP databases and resequencing. On combining the data reported in this study with SNP databases, the most promising target SNPs for GSTT1 association studies are those causing the amino acid changes Asp43Asn, Thr65Met, Thr104Pro and the single nucleotide deletion in exon 4. These gene variants should be analyzed in African--American and Hispanic subjects to increase the predictive capacity of genetic tests. For Caucasians and Oriental subjects, testing for null alleles seems to be sufficient.

Keywords: gene deletion; genotyping; GSTM1; GSTT1; SNPs

Document Type: Research article

DOI: http://dx.doi.org/10.2217/14622416.9.3.359

Affiliations: 1: 1Department of Pharmacology, Medical School, University of Extremadura. Avenida de Elvas sin núúmero, 06071, Badajoz, Spain., Email: jagundez@unex.es

Publication date: 2008-03-01

More about this publication?

• Pharmacogenomics provides the community with an essential resource for keeping abreast of the latest developments in new pharmacogenomic initiatives, emerging technologies for accessing genomic information and the development of novel diagnostic products and strategies.
• Editorial Board
• Information for Authors
• Submit a Paper
• Subscribe to this Title
• Information for Advertisers
• Terms & Conditions
• Information for Librarians
• E-Access Trials
• ingentaconnect is not responsible for the content or availability of external websites

Related content

• In this: publication
• By this: publisher
• In this Subject: Biotechnology ,  Pharmacology ,  Genetics
• By this author: Agúúndez, Joséé AG ;  Ladero, Joséé M

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers