Original Research Article Functional Variability of Glutathione S-Transferases in Basque Populations

Objectives: Glutathione S-transferases (GSTs) are enzymes involved in Phase II reactions. They play a key role in cellular detoxification. Various studies have shown that genes coding for the GST are highly polymorphic and some of these variants are directly associated with a decrease of enzyme activity making individuals more suscepti- ble to different clinical phenotypes. The aim of this study is to investigate the genetic variability of GST genes among human populations. We have focused our attention on the polymorphic variants of the GSTA1, GSTM1, GSTO1, GSTO2, GSTP1, GSTT1, and GSTT2B genes. Methods: These polymorphisms were analyzed in a whole sample of 151 individuals: 112 autochthonous Navarrese Basques, and 39 non-autochthonous Navarrese Basques. DNA extraction from plasma was performed by using the phe- nol:chloroform:isoamylic alcohol method. Genotyping of the gene polymorphisms was performed by PCR Multiplex and the PCR-RFLP method. We applied correspondence analysis and built frequency-maps to compare the genetic structure in worldwide populations. Results: Our results were compared with data available on the Human Genome Diversity Project (HGDP) and on the 1,000 Genomes Project to obtain information on the functional variability of GSTs in Basques. Our data indicated that Basque communities showed a higher differentiation of certain functional GST variants (i.e., GSTM1-positive/null genotype, GSTP1*I105V, and GSTT2B*1/0) than other European and Mediterranean populations. Conclusions: This might account for epidemiological differences in the predisposition to diseases and drug response among Basques and could be used to design and interpret genetic association studies for this particular population. Am. J. Hum. Biol. 00:000-000, 2014. V C 2014 Wiley Periodicals, Inc. The anthropic activities expose human populations on a daily basis to a high number of xenobiotics and toxic com- pounds with consequent biological effects on human health. Therefore, the study of genes involved in cellular protection mechanisms may be used to analyze the inter- action between genetic and environmental factors (Sturchio et al., 2008). The study of genetic polymorphic variants has become crucial to the understanding of the mechanisms underlying significant alterations in detoxifi- cation enzyme activity. Therefore, the identification of the genetic variants associated with significant alterations in coded-protein would provide a better assessment of indi- vidual response to drugs and of the adaptive response to environmental stimuli (Cocozza and Vaccaro, 2005). The enzymes involved in cellular detoxification include acti- vating enzymes, or Phase I proteins, and inactivating enzymes, or Phase II proteins. The Phase I enzymes cata- lyze the insertion of a hydrophilic group to produce highly reactive intermediates that serve as substrates in the sub- sequent conjugation reactions. The Phase II enzymes mediate the link between soluble molecules (e.g., glutathi- one, GSH) with the electrophilic center of the reactive compound in order to make the metabolite free of signifi-