Short Communication Polymorphisms of glutathione S-transferases M1, T1, P1 and A1 genes in the Tunisian population: An intra and interethnic comparative approach Ghada Ben Salah a, ⁎, Fakhri Kallabi a , Sirine Maatoug a , Emna Mkaouar-Rebai a , Amine Fourati b , Faiza Fakhfakh a , Hamadi Ayadi c , Hassen Kamoun a, ⁎ a Laboratory of Human Molecular Genetics, Faculty of Medicine, University of Sfax, Tunisia b Research Unit, Chemical Tunisian Group, Sfax, Tunisia c Centre of Biotechnology, University of Sfax, Tunisia abstract article info Article history: Accepted 21 January 2012 Available online 31 January 2012 Keywords: Glutathione S-transferase Intra/interethnic variability Combined genotypes Tunisian population Genetic polymorphisms in glutathione S-transferases (GSTs) genes might influence the detoxification activ- ities of the enzymes predisposing individuals to cancer risk. Owing to the presence of these genetic variants, inter-individual and ethnic differences in GSTs detoxification capacity have been observed in various popula- tions. Therefore, the present study was performed to determine the prevalence GSTM1*0/*0, GSTT1*0/*0, GSTP1 Ile 105 Val, and GSTA1*A/*B polymorphisms in 154 healthy individuals from South Tunisia, and to com- pare them with those observed in North and Centre Tunisian populations and other ethnic groups. GSTM1 and GSTT1 polymorphisms were analyzed by a Multiplex-PCR approach, whereas GSTP1 and GSTA1 polymor- phisms were examined by PCR-RFLP. The frequencies of GSTM1*0/*0 and GSTT1*0/*0 genotypes were 53.9% and 27.9%, respectively. The genotype distribution of GSTP1 was 47.4% (Ile/Ile), 40.9% (Ile/Val), and 11.7% (Val/Val). For GSTA1, the genotype distribution was 24.7% (*A/*A), 53.9% (*A/*B), and 21.4% (*B/*B). The com- bined genotypes distribution of GSTM1, GSTT1, GSTP1 and GSTA1 polymorphisms showed that thirty one of the 36 possible genotypes were present in our population; eight of them have a frequency greater than 5%. To the best of our knowledge, this is the first report of GSTs polymorphisms in South Tunisian population. Our findings demonstrate the impact of ethnicity and reveal a characteristic pattern for Tunisian population. The molecular studies in these enzymes provide basis for further epidemiological investigations in the pop- ulation where these functional polymorphisms alter therapeutic response and act as susceptibility markers for various clinical conditions. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Glutathione S-transferases (GSTs) are a supergene family of phase-II isoenzymes, play a critical role in providing protection against electrophiles and products of oxidative stress (Guengerich, 2000; Strange et al., 2001). GSTs catalyze the conjugation of glutathi- one to electrophilic compounds, resulting in less reactive and more easily excreted glutathione conjugates. Four major classes of GSTs have been described, based on sequence homology and substrate specificity: μ (GSTM), V (GSTT), π (GSTP), and α (GSTA)(Hayes and Pulford, 1995). Within the GSTM and GSTT classes, GSTM1 and GSTT1 genes ex- hibit deletion polymorphisms, which in the case of homozygozity (GSTM1*0/*0) and (GSTT1*0/*0) lead to the absence of enzyme activity (Zhong et al., 1992). GSTM1 is involved in the detoxification of tobacco related carcinogens, such as epoxides and hydroxylated metabolites of benzo(α)-pyrene (Ketterer et al., 1992). The GSTT1 is involved in the biotransformation of several low molecular weight halogenated toxins such as ethylene oxide, butadiene, which are constituents of tobacco smoke (Guengerich et al., 1995). The GSTM and GSTT deletion poly- morphisms are reported to play a crucial role in cancer susceptibility (Chelbi et al., 2007; Hatagima et al., 2008; Mohr et al., 2003; Okcu et al., 2004; Souiden et al., 2010; Stoehlmacher et al., 2002). Among the GSTP class, GSTP1 gene displays a single nucleotide polymorphism (SNP) (rs 947894) in the coding region at codon 105 (Ile 105 Val), that has been shown to confer lower level of metabolic activity (Watson et al., 1998) associated to cancers (Hohaus et al., 2005; Lakhdar et al., 2010; Okcu et al., 2004; Stoehlmacher et al., 2002). For the GSTA class, the GSTA1 gene shows five SNPs, one of Gene 498 (2012) 317–322 Abbreviations: GSTs, Glutathione S-transferases; GSTM1, Glutathione S-transferase M1; GSTT1, Glutathione S-transferase T1; GSTP1, Glutathione S-transferase P1; GSTA1, Glutathione S-transferase A1; PCR, Polymerase Chain Reaction; RFLP, Restriction frag- ment Length Polymorphism; DNA, Deoxyribonucleic acid; SNP, Single-nucleotide polymorphism. ⁎ Corresponding authors at: Laboratory of Human Molecular Genetics, Faculty of Medicine, University of Sfax, Av. Majida Boulila, Sfax (3029) Tunisia. Tel./fax: + 216 74 461 403x159. E-mail addresses: ghada.bsalah@gmail.com (G. Ben Salah), hassen.kamoun@fmsf.rnu.tn (H. Kamoun). 0378-1119/$ – see front matter © 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.gene.2012.01.054 Contents lists available at SciVerse ScienceDirect Gene journal homepage: www.elsevier.com/locate/gene