Human GST loci as markers of evolutionary forces: GSTO1*E155del
and GSTO1*E208K polymorphisms may be under natural selection induced by
environmental arsenic
Affiliations: Department of Biology, University of Rome "Tor
Vergata", Rome, Italy | Clinical Physiopathology Center, AFaR, "San Giovanni
Calibita" Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy
Note: [] Corresponding author: Maria Fuciarelli, Department of Biology,
University of Rome "Tor Vergata", Via della Ricerca Scientifica 1, 00133 Rome,
Italy. Tel.: +39 0 672 594 346; E-mail: [email protected]
Abstract: Over the last two decades, significant data has been accumulated
linking Glutatione S-Transferases (GSTs) with the development of several
diseases. Contemporary studies have demonstrated the impact of ethnicity on GST
allele frequencies. The aim is to verify if the variability of GST genes
reflects population demographic history or rather selective pressures. GST genes (GSTM1, GSTO1 GSTO2, GSTT1) were analysed in three
Ecuadorian populations (Cayapas, n=114; Colorados, n=104; African-Ecuadorian,
n=77) and compared with HapMap data. GST SNPs were determined using the
PCR-RFLP method while GST null phenotype was determined using a Multiplex PCR.
The population relationship achieved using GSTM1 positive/null,
GSTO1*A140D, GSTO2*N142D and GSTT1 positive/null are in agreement with the data
obtained using neutral polymorphisms: Amerindians are close to Asian
populations and African-Ecuadorians to African populations. To what concerns
GSTO1*del155 and GSTO1*K208 variants, allele frequencies never exceeded 10%,
showing no significant differences in the Ecuadorian groups and in worldwide
populations. The features of GSTO1*del155 and GSTO1*K208 variants and their
association with arsenic biotransformation deficiency suggest the presence of a
selection mechanism towards these loci. In particular, this hypothesis is
strengthened by a possible linkage between these alleles and the susceptibility
of arsenic-induced male infertility.
