Genetic variability of glutathione S-transferase enzymes in human populations: Functional inter-ethnic differences in detoxification systems

Polimanti, Renato; Carboni, Cinzia; Baesso, Ilenia; Piacentini, Sara; Iorio, Andrea; Stefano, G. F. De; Fuciarelli, Maria

doi:10.1016/j.gene.2012.09.113

Cited by 43 publications

(34 citation statements)

References 38 publications

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“…This observation of other than Africa split in this study has been reported here in agreement to the concepts of later migration of the populations in regions other than Africa [60, 64]. In conclusion, the data of seven patterns for GST M1-T1 null allele frequency from Xhosa tribe (I), Zimbabwe (II), Ethiopia (III), Egypt (IV), Afghanistan (V), Caucasian (VI) and South Indian Andhra Pradesh (VII) reported in this study compare constructively with the earlier studies that suggested the PAs of relatively recent origin show comparatively small genetic differences and high genetic affinity among them [11, 46, 52, 58]. Findings of these seven patterns (I-VII) for GST M1-T1 null allele frequency reported here, would shed some light to address the missing link in most of the genomic epidemiological studies that lacks conclusive risk association [9, 16, 17].…”

Section: Discussionsupporting

confidence: 83%

“…To address the extent of diversity in allele frequency distribution among populations from different ethnicity, region, country or continent is difficult, nevertheless understanding this phenomenon is inevitable [8, 11, 16, 17] and recent advances in the molecular techniques excel the perspective of inter-individual genetic variations in GAHPs. Allele frequencies of large number of neutral markers or of even few candidate markers that duplicate or decay to favor new environments and lead to rapid adaptations are often used for investigating the patterns [58].…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies in the recent past have hypothesized the difference in metabolic rate of M1 and T1 classes of GST as the risk factor associated to cancers of bladder, pancreas, upper aero digestive tract, lung, esophageal, head-neck, melanoma and also in Balken endemic nephropathy patients [4–9]. Further, the inter-individual difference in drug disposition and efficacy has been investigated by various authors [10] and the observed frequency distributions of GST M1-T1 genotypes among different populations are reported as ethnic or PAs dependent [10, 11]. Drugs are the major hope of remedy for the people around the globe with various metabolic and genetic disorders but the scenario in the past was found distressed as the effectiveness of the drugs were reported by the influence of the unidentified polymorphic patterns observed in drug metabolism genes among different ethnics or PAs [11–13].…”

Section: Introductionmentioning

confidence: 99%

“…Further, the inter-individual difference in drug disposition and efficacy has been investigated by various authors [10] and the observed frequency distributions of GST M1-T1 genotypes among different populations are reported as ethnic or PAs dependent [10, 11]. Drugs are the major hope of remedy for the people around the globe with various metabolic and genetic disorders but the scenario in the past was found distressed as the effectiveness of the drugs were reported by the influence of the unidentified polymorphic patterns observed in drug metabolism genes among different ethnics or PAs [11–13]. Though researchers from different PAs are interested in analyzing the frequencies of GST M1 and T1 null genotypes and their possible risk association with various disorders, they are not able to report conclusive association in all major PAs [14, 15].…”

Section: Introductionmentioning

confidence: 99%

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GST M1-T1 null Allele Frequency Patterns in Geographically Assorted Human Populations: A Phylogenetic Approach

et al. 2015

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Genetic diversity in drug metabolism and disposition is mainly considered as the outcome of the inter-individual genetic variation in polymorphism of drug-xenobiotic metabolizing enzyme (XME). Among the XMEs, glutathione-S-transferases (GST) gene loci are an important candidate for the investigation of diversity in allele frequency, as the deletion mutations in GST M1 and T1 genotypes are associated with various cancers and genetic disorders of all major Population Affiliations (PAs). Therefore, the present population based phylogenetic study was focused to uncover the frequency distribution pattern in GST M1 and T1 null genotypes among 45 Geographically Assorted Human Populations (GAHPs). The frequency distribution pattern for GST M1 and T1 null alleles have been detected in this study using the data derived from literatures representing 44 populations affiliated to Africa, Asia, Europe, South America and the genome of PA from Gujarat, a region in western India. Allele frequency counting for Gujarat PA and scattered plot analysis for geographical distribution among the PAs were performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of the PAs were computed in Seqboot, Gendist program of Phylip software package (3.69 versions) and Unweighted Pair Group method with Arithmetic Mean in Mega-6 software. Allele frequencies from South African Xhosa tribe, East African Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian Afghanistan and South Indian Andhra Pradesh have been identified as the probable seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null genotypes. The patternized null allele frequencies demonstrated in this study for the first time addresses the missing link in GST M1-T1 null allele frequencies among GAHPs.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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GST M1-T1 null Allele Frequency Patterns in Geographically Assorted Human Populations: A Phylogenetic Approach

et al. 2015

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“…Its classification is based on substrate specificity and amino acid sequence similarity and encompasses eight classes: GSTA (alpha), GSTK (kappa), GSTM (mu), GSTP (pi), GSTS (sigma), GSTT (theta), GSTO (omega), and GSTZ (zeta) [19, 20]. This family presents a strong genetic variability among human populations and its molecular diversity is determined by ethnic background [21]. The null polymorphic variants (homozygous for nonfunctional allele) GSTM1 and GSTT1 have been associated with a variety of health problems, such as high blood pressure in subjects from India and with the development of inflammatory bowel disease in non-Jewish patients from Israel [22, 23].…”

Section: Gst and Mercury Exposurementioning

confidence: 99%

Biomarkers of Mercury Exposure in the Amazon

Castro

Lima

2014

BioMed Research International

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Mercury exposure in the Amazon has been studied since the 1980s decade and the assessment of human mercury exposure in the Amazon is difficult given that the natural occurrence of this metal is high and the concentration of mercury in biological samples of this population exceeds the standardized value of normality established by WHO. Few studies have focused on the discovery of mercury biomarkers in the region's population. In this way, some studies have used genetics as well as immunological and cytogenetic tools in order to find a molecular biomarker for assessing the toxicological effect of mercury in the Amazonian population. Most of those studies focused attention on the relation between mercury exposure and autoimmunity and, because of that, they will be discussed in more detail. Here we introduce the general aspects involved with each biomarker that was studied in the region in order to contextualize the reader and add information about the Amazonian life style and health that may be considered for future studies. We hope that, in the future, the toxicological studies in this field use high technological tools, such as the next generation sequencing and proteomics skills, in order to comprehend basic questions regarding the metabolic route of mercury in populations that are under constant exposure, such as in the Amazon.

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