Evaluation of the association between null genotypes of glutathione-S-transferases and Behcet’s disease

Department of Molecular Biology, Faculty of Science and Arts, Manisa Celal Bayar University, Manisa, Turkey.
Archives for Dermatological Research (Impact Factor: 1.9). 02/2006; 297(7):289-93. DOI: 10.1007/s00403-005-0617-1
Source: PubMed


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.

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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). "
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    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.
    Full-text · Article · Jan 2013
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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. "
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    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.
    Full-text · Article · Jan 2010 · Genetics and molecular research: GMR
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    ABSTRACT: Vitiligo is an acquired pigmentary disorder of the skin involving melanocyte dysfunction. It has been reported that melanocyte impairment could be related to increased oxidative stress. The glutathione S-transferases (GSTs) are group of polymorphic enzymes that are important in protection against oxidative stress. To find the relationship between GSTM1 and GSTT1 polymorphisms with vitiligo susceptibility, GSTM1 and GSTT1 (homozygous deletion vs. non-deleted) polymorphisms between vitiligo patients (n=310) and healthy controls (n=549) were analyzed. We observed significant association in null alleles of the GSTM1 (P<0.001, OR=2.048, 95% CI=1.529-2.743). GSTM1 null type was also statistically different between two vitiligo subtypes and controls (Focal P<0.001, OR=2.224, 95% CI=1.499-3.298; Generalized P=0.001, OR=1.974, 95% CI=1.342-2.904). However, no significant association in GSTT1 (P=0.869, OR=1.024, 95% CI=0.775-1.353) was observed with vitiligo. In combined analysis of GSTM1 and GSTT1, both null type and GSTM1/GSTT1 (null/present) group showed significant differences between controls and vitiligo patients. These results suggest that GSTM1 null type might be associated with vitiligo susceptibility in Korean population.
    No preview · Article · Jun 2007 · Life Sciences
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