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Nutrigenomics for Sport and Exercise Performance
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Nanci S. Guest, Marc Sicova, Ahmed El-Sohemy
The GSTT1 gene encodes a protein in the glutathione S-transferase enzyme, which mitigates oxidative stress through vitamin C status (23). Circulating levels of vitamin C can be modified due to a SNP in the GSTT1 (Ins or Del) gene. Those with the Del/Del genotype of GSTT1 possess an elevated risk for vitamin C deficiency compared to those with the Ins allele (83). Vitamin C is measured through ascorbic acid, and deficiencies are likely when intake is low. Vitamin C deficiency is characterized by the damage of healthy tissues, reduced connective tissue repair, and early exercise fatigue (23, 83). Athletes who possess the Ins allele of GSTT1 are recommended to not consume vitamin C supplements, as it may negatively interfere with positive training adaptions that occur with low-level exercise-induced muscle damage (45, 65). Athletes can consume 250 mg daily without interfering with training adaptations (126). Those with the Del/Del genotype should ensure they consume adequate vitamin C and may also supplement to ensure optimal collagen production to repair muscles and tendons (133).
Gene–Nutrient Interaction
Published in David Heber, Zhaoping Li, Primary Care Nutrition, 2017
Null genotypes for GSTM1 and GSTT1 occur commonly and result in the absence of the respective enzymes. Both of these enzymes are involved in the metabolism of environmental carcinogens and reactive oxygen species. Thus, until recently, the primary hypothesis has been that individuals with the GST null genotypes are at higher risk for cancer because of reduced capacity to dispose of activated carcinogens. Numerous epidemiologic studies have focused on interactions between these polymorphisms and carcinogen exposure. Now, researchers are also studying relationships between GST polymorphisms and exposure to preventive agents (i.e., ITCs), with the hypothesis being that because ITCs are metabolized by GST, polymorphisms associated with reduced GST activity will result in longer circulating half-lives of ITCs and potentially greater chemoprotective effects of cruciferous vegetables (Lampe et al. 2000).
Biomarkers of Toxicant Susceptibility
Published in Anthony P. DeCaprio, Toxicologic Biomarkers, 2006
GSTT1: In addition to the null polymorphism of locus GSTM1, another null polymorphism has been found in the class of θ transferases to locus T1 (wild normal allele GSTT1*1, null allele GSTT1*0). The frequency of homozygotic GSTT1*0 (*0/*0) varies in several populations, 16% in the British and 38% in Nigerians. It is difficult to predict the biological consequences of genotype GSTT1 null, since this enzyme has both detoxifying and activating properties, which affect many environmental pollutants. From a genotoxic point of view, although GSTT1 detoxifies monohalomethanes (e.g., methyl bromide) and epoxides of the alkenes, ethylene and butadiene, it activates methylene chloride and some bifunctional alkylating agents. Human erythrocytes, unlike those of rodents, express GSTT1, and this activity allows red blood cells to sequester the reactive conjugates resulting from the “toxifying” activity of GSTT1, thus preventing their genotoxic attack on DNA (20).
Evaluation of molecular markers GSTM1 and GSTT1 and clinical factors in breast cancer: case-control study and literature review
Published in Xenobiotica, 2021
Stéphanie Piacenti dos Santos, Sabrina Sayuri Morissugui, Ana Paula D’Alarme Gimenez Martins, Glaucia Maria de Mendonça Fernandes, Anelise Russo, Ana Lívia Silva Galbiatti-Dias, Márcia Maria Urbanin Castanhole-Nunes, José Luis Esteves Francisco, Érika Cristina Pavarino, Eny Maria Goloni-Bertollo
We did not observe an association between the GSTM1 null or the GSTT1 null genotypes and an increased risk for breast cancer were not different from those described in previous publications (Chacko et al. 2005; Unlü et al. 2008; Sohail et al. 2013; Zgheib et al. 2013; Al-Eitan et al. 2019; Kalacas et al. 2019) including some others involving subjects from Brazil (DA Fonte DE Amorim et al. 2002; Linhares et al. 2005; Torresan et al. 2008; DE Aguiar et al. 2012). However, in others studies the null GSTM1 and GSTT1 was associated with breast cancer risk (Ramalhinho et al. 2011, 2012; Miao et al. 2020). In contrast, two other studies showed that GSTT1 null and GSTM1 null genotypes conferred less reduced risk to breast cancer (Parl 2005; Kaushal et al. 2010). A comparative summary of the results of this study with published literature since 1998 was presented in the Table 4.
Polymorphisms in xenobiotic metabolism-related genes in patients with hepatocellular carcinoma: a case–control study
Published in Xenobiotica, 2021
Gislaine Dionísio Ferreira, Glaucia Maria de Mendonça Fernandes, Camila Penteado, Vivian Romanholi Cória, Ana Lívia da Silva Galbiatti-Dias, Anelise Russo, Márcia Maria Urbanin Castanhole-Nunes, Renato Ferreira da Silva, Rita de Cássia Martins Alves da Silva, Érika Cristina Pavarino, Mariangela Torreglosa Ruiz Cintra, Eny Maria Goloni-Bertollo
We did not observe any difference in the distribution of the GSTP1.Ala114Val mEH Tyr113His (T337C) and His139Arg polymorphisms, but we found an imbalance for the GSTM1 and GSTT1 polymorphisms. As is common in the analysis of genotyping data, the p-values of the polymorphisms in the linkage disequilibrium are dependent (Hao and Storey 2019). When assessing the level of statistical significance, this should be considered (Hao and Storey 2019). GSTT1 and GSTM1 are members of the GST superfamily and can present polymorphic variants with complete deletion, which causes a decrease in enzymatic activity (Tang et al. 2014), leading to damage in the efficient detoxification of toxic metabolites. The GSTT1 gene is located on chromosome region 22q11.2 (Zheng et al.2002, Ye et al. 2006, Chen et al. 2014). Conversely, the GSTM1 gene is mapped to chromosome region 1p13.1 (Pavanello and Clonfero, 2000b, 2000a, Vogl et al. 2004), and the GSTP1 gene is located on chromosome region 11q13. It can present a nucleotide substitution (C→T) at position 341, resulting in the substitution of the amino acid cysteine for thymine in the protein. This alteration substantially reduces the activity of these enzymes and induces higher adduct levels in the liver tissues (Chen et al.2010). EPHX1 is an important enzyme in the microsomal defence mechanism against the toxicity of xenobiotics in phase II and plays essential physiological roles (Václavíková et al. 2015).
Genomics of Detoxification: How Genomics can be Used for Targeting Potential Intervention and Prevention Strategies Including Nutrition for Environmentally Acquired Illness
Published in Journal of the American College of Nutrition, 2020
Sharon R. Hausman-Cohen, Lee J. Hausman-Cohen, Grant E. Williams, Carol E. Bilich
As previously discussed, GSTP1 is a vital component of the detox system via attaching toxicants, carcinogens and other offending substances to glutathione so they can be eliminated in the urine, feces or sweat (Figure 1). GSTT1 and GSTM1 are also members of this GST (glutathione S-transferase) gene superfamily and are heavily involved in our glutathione conjugation detox system. These 2 genes are unique in that a large percentage of the population is without the protein product due to having a complete deletion of the gene (17). When the gene is absent on both the chromosomes inherited from an individual's mother and father, it is called a GSTM1 or GSTT1 null individual. Those that have the null genotype lack enzyme activity for the respective gene (17) and thus have impaired detox/toxicant clearance (12) as well as impaired heavy metal clearance- including mercury and lead- and enhanced susceptibility to oxidative stress (18).