Cytochrome 1A1 (CYP1A1), glutathione transferase M1 (GSTM1), and glutathione transferase T1 (GSTT1) catalyze the bioactivation and detoxification of a wide variety of xenobiotic compounds that are mutagenic and/or carcinogenic (e.g., polycyclic aromatic hydrocarbons). Genetic polymorphisms of these metabolizing enzymes have been shown to affect individual susceptibility to environmental carcinogenic compounds. Although several studies have been published on the relationship between CYP1A1*2C, GSTM1*0, or GSTT1*0 polymorphism and cancer, not all findings can be extrapolated to other populations because of interethnic variability. Here, we investigate the frequency of CYP1A1*2C, GSTM1*0, or GSTT1*0 in a sample of Mexican Mestizos. We find that the frequency of GSTM1*0 is 0.335, that of GSTT1*0 is 0.121, and that of GSTM1*0 + GSTT1*0 is 0.023. The frequency of CYP1A1*2C is 0.54. Similitude analysis sets the Latin American populations in a common cluster near the Asian population, suggesting that the CYP1A1*2C polymorphism may have originated from this population and suffered a founder effect in the American population. Analysis of CYP1A1*2C, GSTM1*0, and GSTT1*0 haplotypes reveals that 35% of the population has some combination of risk genotypes. Taken together, these results point to a high susceptibility of the Mexican Mestizo population to the effects of environmental carcinogens.
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http://dx.doi.org/10.3378/1534-6617-80.4.457 | DOI Listing |
Chemosphere
November 2015
Andalusian School of Public Health (EASP), Granada, Spain; Institute of Biosanitary Research (ibs.GRANADA), University Hospitals/University of Granada, Granada, Spain; CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain.
Polymorphisms in genes encoding xenobiotic-metabolizing enzymes (XME) are important parameters accounting for the wide inter-individual variability to environmental exposures. Paraoxonase-1 (PON1), butyrylcholinesterase (BChE) and Cytochrome-P450 constitute major classes of XME involved in the detoxification of pesticide chemicals, in particular organophosphates. This study explored the allelic frequency, linkage disequilibrium and haplotype analysis of ten common polymorphic variants of seven key genes involved in organophosphate metabolism (BCHE-K, BCHE-A, PON1 Q192R, PON1 L55M, PON1 -108C/T, CYP2C19 G681A, CYP2D6 G1846A, CYP3AP1 -44G/A, GSTM1∗0 and GSTT1∗0) in a children population living near an intensive agriculture area in Spain.
View Article and Find Full Text PDFBull Exp Biol Med
November 2012
Angarsk [corrected] Affiliated Department of East Siberian Center of Human Ecology, Siberian Division of the Russian Academy of Medical Sciences, Irkutsk, Russia.
The relationship between blood levels of HSP72, HSP72+HSP73, and HSP90 and genotypes of three polymorphisms of the HSP70 family, HSPA1L (2437T/C) and HSPA1B (2074G/C and 1267A/G) as well as GSTT1 and GSTM1 polymorphisms was studied in 82 men chronically exposed to mercury. Of these, 40 men were exposed to mercury for more than 10 years (group 1) and 42 developed chronic mercuric intoxication (group 2). The groups differed significantly by TT (p=0.
View Article and Find Full Text PDFAim: The aim of the present study was to test the association between genetic polymorphisms with functional effects on redox regulation: Ala16Val of manganese superoxide dismutase (MnSOD or SOD2), polymorphic deletions of glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and Ile105Val of the GSTP1 and carotid atherosclerosis in patients with type 2 diabetes.
Methods: The study enrolled 287 subjects with type 2 diabetes. Carotid atherosclerosis was quantified by ultrasonography as carotid intima-media thickness (CITM), plaque score from 0 to 6 and plaque type from 1 to 5.
Am J Clin Nutr
September 2011
School of Public Health, University of California at Berkeley, 94720-7360, USA.
Background: Glutathione S-transferases (GSTs) detoxify environmental chemicals and are involved in oxidative stress pathways. Deletion polymorphisms affect enzyme activities and have been associated with risk of disease.
Objective: The objective was to clarify whether biomarkers of oxidation, antioxidation, inflammation, and nutritional factors differ by GST genotype in healthy adults.
Clin Exp Rheumatol
September 2009
Institute of Biochemistry, Faculty of Medicine, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Objectives: Glutathione S-transferases (GST); GST-mu1 (GSTM1), GST-pi1 (GSTP1) and GST-theta1 (GSTT1) have peroxidase activity towards cytotoxic metabolites produced in inflammatory reactions, the main feature of rheumatoid arthritis (RA). Genetic polymorphisms in GSTM1, GSTP1 and GSTT1 modify the enzyme conjugation capacity and may be associated with the activity of RA.
Methods: A genotyping approach was used to analyze GSTM1-0, GSTT1-0 and GSTP1 Ile105Val and Ala114Val polymorphisms in 213 RA patients.
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