Evaluation of the association between null genotypes of glutathione-S-transferases and Behcet’s disease
ABSTRACT Glutathione S-transferases (GST) play an important role in oxidative stress related syndromes. An imbalance of the oxidant and antioxidant systems is important in the pathogenesis of Behcet's disease (BD). The objective of this study was to evaluate the association of null genotypes of GST-M1 and GST-T1 with BD since some preliminary molecular genetic data were recently published. Ninety-four Turkish BD patients (42 male, 52 female, 37.1+/-10.4 years) and 140 healthy volunteers (70 male, 70 female, 36.8+/-11.7 years) matched for age and gender with the patients as the control group were included in the study. Distributions of GST-M1 and GST-T1 genotypes were determined by multiplexed PCR using three sets of primers for GST-M1, GST-T1, and beta-globulin genes. There was no association between BD and the frequencies of GST-M1 and GST-T1 null genotypes when compared to controls by separate analysis. However, by cross and pooled combination analysis there was a significant association between the frequencies of pooled GSTs with one or both null genotypes in BD and controls. This is the first evidence that the association between the frequencies of GST-M1 and GST-T1 null genotypes and BD might be dependent on the interaction of multiple null allele polymorphisms rather than a single null allele of GST-M1 and GST-T1.
- SourceAvailable from: Amal Saad-Hussein
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- "In humans, seven distinct gene families encode soluble GSTs; the glutathione S-transferases (GST) expressed in human tissue comprise the alpha (A), mu (M), pi (P), theta (T), kappa (K), omega (O) and zeta (Z) gene families (Yu et al., 2011 and Uzunoğlu et al., 2006). Among them, four are mainly expressed in human tissues: GSTA, GSTM, GSTT, and GSTP (Wang et al., 2010) GSTM1, GSTT1, and GSTP1 genes have been extensively examined in association with risk of cancer and clinical outcomes of cancer patients (Yu et al., 2011) Both GSTM1 and GSTT1 enzymes are known to catalyze the detoxification of reactive oxygen and lipid peroxidation products (Uzunoğlu et al., 2006). Polymorphic deletion variants in the GSTM1 and GSTT1 genes produce either a functional enzyme (non-deletion alleles or heterozygous deletion, GSTM11 and GSTT11) or result in the complete absence of the enzyme (homozygous deletion alleles, GSTM1null and GSTT1null) (Xiao and Ma 2012). "
ABSTRACT: Little is known whether occupational exposure to aflatoxin might have a potential hazard. The present work aimed to study the hepatotoxic effects of occupational exposure to AFB1 as a metabolite of high Aspergillus concentrations in the working environments, and the polymorphism of GST gene in exposed workers. The study was performed on 97 flour mill workers exposed to high Aspergillus concentrations and 78 non-exposed controls. The levels of AFB1/Alb (ng/g), AST and ALT of the workers were significantly higher than the controls, while there was no significance difference in the ALP levels between the two groups. The present results revealed that AFB1/Alb levels were significantly higher in the workers with the different GST alleles compared to the control groups. Additionally, AFB1/Alb levels were significantly higher in the workers with GSTT1 compared to the workers with different GST alleles (GSTM1 and Null (GSTT1&GSTM1)) and the controls with Null (GSTT1&GSTM1) alleles. In conclusion, occupational exposure to the high concentrations of Aspergillus in the workplace may cause an increase in the AFB1/Alb and the liver enzymes in flour mill workers. These results also showed that the Null (GSTM1 & GSTT1) alleles are the most common type in the studied population. The workers with GSTT1 have lower ability to detoxify AFB1.
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- "Glutathione S-transferases can work as endogenous antioxidants to protect cells from oxidative stress. It is observed that the GSTT1 and GSTM1 null genotypes cause a decrease in enzyme activity and the oxidative stress inactivation is reduced especially in people with the GSTM1 null genotype (Van der Hel et al., 2003; Uzunoğlu et al., 2006). As far as we know, up to this date, there has been no study investigating ROP progress with GSTT1 and GSTM1 polymorphisms. "
ABSTRACT: One of the most frequently observed causes of blindness in infancy is the pathogenesis known as retinopathy of prematurity (ROP). Angiotensin-converting enzyme (ACE) is a vital enzyme in the renin-angiotensin-aldosterone system; it is involved in the development of cardiovascular system diseases linked to I/D polymorphism of the ACE gene. Glutathione-S-transferase enzyme (GST) is one of the most important regulating components of the antioxidant system; there are indications that certain polymorphisms of GST genes (GSTT1, GSTM1), especially the null genotypes, increase the tendency for oxidative stress diseases. We investigated a possible correlation between ACE gene I/D and GSTT1 and GSTM1 gene polymorphisms in 56 prematures suffering from ROP and a control group composed of 48 prematures without ROP in a hospital in Turkey. PCR was used to detect the ACE I/D, GSTT1 and GSTM1 gene polymorphisms. Genotype was determined based on bands formed on agarose gel electrophoresis. We found no significant differences in genotype frequency of the ACE I/D, GSTT1 and GSTM1 genes between normal subjects and patients with ROP. Our results do not support an association of ACE I/D, GSTT1 and GSTM1 gene polymorphisms with risk for ROP.Genetics and molecular research: GMR 01/2010; 9(4):2131-9. DOI:10.4238/vol9-4gmr887 · 0.78 Impact Factor
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ABSTRACT: Several factors participate in the pathogenesis of Alzheimer's disease (AD), including free radicals, which when out of balance with their antioxidant capacity contribute to the oxidative stress process and neuronal death. The glutathione S-transferase (GST) polymorphisms are associated with the organism detoxification capacity and can help with the identification of sub-groups that present susceptibility to the development of AD. The aim of this study was to analyze the association of GSTs, including GSTP1, GSTT1 and GSTM1 and apolipoprotein E (apoE) with AD and the distribution of these polymorphisms in the first-degree relatives of patients. For this, 41 patients with AD, 24 elderly without cognitive deficits (control group), 109 relatives of patients with AD and 41 relatives of controls were studied. A sample of peripheral blood was drawn for leukocyte DNA extraction. The genetic polymorphisms were analyzed by PCR-RFLP. There was a significantly higher frequency of the 4 allele in the patients (0.21) and in their relatives (0.25) when compared to controls (0.04; p=0.01) and their relatives (0.03; p<0.0001). The V allele of the GSTP1 polymorphism was higher in patients compared to controls (0.35 and 0.19, respectively; p=0.04). In contrast, the presence of the GSTT1 polymorphism prevailed in controls (79%) and their relatives. The V allele may be a risk factor for AD, mainly in the presence of the apoE 4 allele, while the presence of GSTT1 may indicate protection against the disease.Clinical Chemistry and Laboratory Medicine 01/2008; 46(4):439-45. DOI:10.1515/CCLM.2008.102 · 2.71 Impact Factor