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  1. Fulltext Rapid birth-death evolution and positive selection in detoxification-type glutathione S-transferases in mammals
    Tan HM, Low WY
    PLoS One, 2018;13(12):e0209336.
    PMID: 30586459 DOI: 10.1371/journal.pone.0209336
    Glutathione S-Transferases (GSTs) are phase II detoxification enzymes that may have evolved in response to changes of environmental substrates. GST genes formed a multigene family and in mammals, there are six classes known as Alpha, Mu, Omega, Pi, Theta, and Zeta. Recent studies in phase I detoxification system specifically the cytochrome P450s provided a general explanation on why genes from a common origin such as those in a multigene family have both phylogenetically stable and unstable genes. Genes that participate in core functions of organisms such as development and physiology are stable whereas genes that play a role in detoxification are unstable and evolve in a process known as birth-death evolution, which is characterised by frequent gene gains and losses. The generality of the birth-death model at explaining the evolution of detoxification enzymes beyond the phase I enzyme has not been comprehensively explored. This work utilized 383 Gst genes and 300 pseudogenes across 22 mammalian species to study gene gains and losses. GSTs vary greatly in their phylogenetic stability despite their overall sequence similarity. Stable Gst genes from Omega and Zeta classes do not show fluctuation in gene numbers from human to opossum. These genes play a role in biosynthesis related functions. Unstable genes that include Alpha, Mu, Pi and Theta undergo frequent gene gain and loss in a process known as birth-death evolution. Gene members of these four classes are well known for their roles in detoxification. Our positive selection screen identified five positively selected sites in mouse GSTA3. Previous studies showed two of these sites (108H and 208E) were biochemically tested as important residues that conferred catalytic activity against the toxic aflatoxin B1-8,9-epoxide. The functional significance against aflatoxin of the remaining three positively selected sites warrant further investigation.
    Matched MeSH terms: Glutathione Transferase/genetics*
  2. Fulltext Association of GSTM1 and GSTT1 with ageing in auto repair shop workers
    Eshkoor SA, Marashi SJ, Ismail P, Rahman SA, Mirinargesi M, Adon MY, et al.
    Genet. Mol. Res., 2012;11(2):1486-96.
    PMID: 22653598 DOI: 10.4238/2012.May.21.5
    We evaluated the possible influence of glutathione S-transferase mu (GSTM1) and glutathione S-transferase theta (GSTT1) genes on genetic damage due to occupational exposure, which contributes to accelerate ageing. This study was conducted on 120 car auto repair workshop workers exposed to occupational hazards and 120 controls without this kind of exposure. The null and non-null genotypes of GSTM1 and GSTT1 genes were determined by multiplex PCR. Micronucleus frequency, Comet tail length and relative telomere length differences between the null and non-null genotypes of the GSTM1 gene were significantly greater in the exposed group. Lack of GSTT1 did not affect the damage biomarkers significantly (P > 0.05), while lack of GSTM1 was associated with greater susceptibility to genomic damage due to occupational exposure. It was concluded that early ageing is under the influence of these genes and the environmental and socio-demographic factors. Duration of working time was significantly associated with micronucleus frequency, Comet tail length and relative telomere length.
    Matched MeSH terms: Glutathione Transferase/genetics*
  3. PARTICIPATION OF Y89 AND Y97 IN THE CONJUGATING ACTIVITY OF Drosophila melanogaster GLUTATHIONE S-TRANSFERASE D3 (DmGSTD3)
    Vignesvaran K, Alias Z
    Arch Insect Biochem Physiol, 2016 Jul;92(3):210-21.
    PMID: 27075600 DOI: 10.1002/arch.21332
    Drosophila melanogaster glutathione S-transferase D3 (DmGSTD3) has a shorter amino acid sequence as compared to other GSTs known in the fruit flies. This is due to the 15 amino acid N-terminal truncation in which normally active amino acid residue is located. The work has made use of homology modeling to visualize the arrangement of amino acid side chains in the glutathione (GSH) substrate cavity. The identified amino acids were then replaced with amino acids without functional groups in the side chains and the mutants were analyzed kinetically. Homology modeling revealed that the side chains of Y89 and Y97 were shown facing toward the substrate cavity proposing their possible role in catalyzing the conjugation. Y97A and Y89A GSH gave large changes in Km (twofold increase), Vmax (fivefold reduction), and Kcat /Km values for GSH suggesting their significant role in the conjugation reaction. The replacement at either positions has not affected the affinity of the enzyme toward 1-chloro-2,4-dinitrobenzene as no significant change in values of Kmax was observed. The replacement, however, had significantly reduced the catalytic efficiency of both mutants with (Kcat /Km )(GSH) and (Kcat /Km )(CDNB) of eight- and twofold reduction. The recombinant DmGSTD3 has shown no activity toward 1,2-dichloro-4-nitrobenzene, 2,4-hexadienal, 2,4-heptadienal, p-nitrobenzyl chloride, ethacrynic acid, and sulfobromophthalein. Therefore, it was evident that DmGSTD3 has made use of distal amino acids Y97 and Y89 for GSH conjugation.
    Matched MeSH terms: Glutathione Transferase/genetics*
  4. Fulltext Analysis of selected glutathione S-transferase gene polymorphisms in Malaysian type 2 diabetes mellitus patients with and without cardiovascular disease
    Etemad A, Vasudevan R, Aziz AF, Yusof AK, Khazaei S, Fawzi N, et al.
    Genet. Mol. Res., 2016 Apr 07;15(2).
    PMID: 27173202 DOI: 10.4238/gmr.15025845
    Type 2 diabetes mellitus (T2DM) is believed to be associated with excessive production of reactive oxygen species. Glutathione S-transferase (GST) polymorphisms result in decreased or absent enzyme activity and altered oxidative stress, and have been associated with cardiovascular disease (CVD). The present study assessed the effect of GST polymorphisms on the risk of developing T2DM in individuals of Malaysian Malay ethnicity. A total of 287 subjects, consisting of 87 T2DM and 64 CVD/T2DM patients, as well as 136 healthy gender- and age-matched controls were genotyped for selected polymorphisms to evaluate associations with T2DM susceptibility. Genomic DNA was extracted using commercially available kits, and GSTM1, GSTT1, and α-globin sequences were amplified by multiplex polymerase chain reaction. Biochemical parameters were measured with a Hitachi autoanalyzer. The Fisher exact test, the chi-square statistic, and means ± standard deviations were calculated using the SPSS software. Overall, we observed no significant differences regarding genotype and allele frequencies between each group (P = 0.224 and 0.199, respectively). However, in the combined analysis of genotypes and blood measurements, fasting plasma glucose, HbA1c, and triglyceride levels, followed by age, body mass index, waist-hip ratio, systolic blood pressure, and history of T2DM significantly differed according to GST polymorphism (P ˂ 0.05). Genetically induced absence of the GSTT1 enzyme is an independent and powerful predictor of premature vascular morbidity and death in individuals with T2DM, and might be triggered by cigarette smoking's oxidative effects. These polymorphisms could be screened in other ethnicities within Malaysia to determine further possible risk factors.
    Matched MeSH terms: Glutathione Transferase/genetics*
  5. Glutathione-S-transferase (GST) polymorphism among ethnic groups in Singapore with report of additional alleles at loci 1 and 2
    Bhattacharyya SP, Saha N, Wee KP
    Gene Geogr, 1989 Apr;3(1):21-6.
    PMID: 2487053
    Glutathione S-transferases (GST; E.C.2.5.1.18) were phenotyped by starch gel electrophoresis in post-mortem liver samples from 683 unrelated subjects of both sexes. 305 were Chinese, 185 Indians, 147 Malays and 46 from other racial groups of South-East Asia. GST1 and GST2 were found to be polymorphic in these populations. Additional alleles (GST1*3 and GST2*O) were observed at low frequency in all the ethnic groups. The frequency of GST1*1 was lower and that of GST1*2 was higher in Indians and Malays as compared to Chinese. GST1*0 and GST1*3 frequencies were similar in all these ethnic groups. The gene frequencies of the alleles of the GST2 locus varied significantly in the population studied. GST2*0 frequency was significantly higher in Indians than in Chinese and Malays, while the lowest frequency of GST2*1 was found in the Indians. GST2*2 frequency was higher in the Malays than in Chinese and Indians. GST1 and GST2 phenotype distributions were in agreement with Hardy-Weinberg equilibrium in all the ethnic groups studied. Sex made no significant difference in the phenotype distribution.
    Matched MeSH terms: Glutathione Transferase/genetics*
  6. Molecular cloning and expression of five glutathione S-transferase (GST) genes from Banana (Musa acuminata L. AAA group, cv. Cavendish)
    Wang Z, Huang S, Jia C, Liu J, Zhang J, Xu B, et al.
    Plant Cell Rep, 2013 Sep;32(9):1373-80.
    PMID: 23652818 DOI: 10.1007/s00299-013-1449-7
    KEY MESSAGE: Three tau class MaGSTs responded to abiotic stress, MaGSTF1 and MaGSTL1 responded to signaling molecules, they may play an important role in the growth of banana plantlet. Glutathione S-transferases (GST) are multifunctional detoxification enzymes that participate in a variety of cellular processes, including stress responses. In this study, we report the molecular characteristics of five GST genes (MaGSTU1, MaGSTU2, MaGSTU3, MaGSTF1 and MaGSTL1) cloned from banana (Musa acuminate L. AAA group, cv. Cavendish) using a RACE-PCR-based strategy. The predicted molecular masses of these GSTs range from 23.4 to 27.7 kDa and their pIs are acidic. At the amino acid level, they share high sequence similarity with GSTs in the banana DH-Pahang (AA group) genome. Phylogenetic analysis showed that the deduced amino acid sequences of MaGSTs also have high similarity to GSTs of other plant species. Expression analysis by semi-quantitative RT-PCR revealed that these genes are differentially expressed in various tissues. In addition, their expression is regulated by various stress conditions, including exposure to signaling molecules, cold, salinity, drought and Fusarium oxysporum f specialis(f. Sp) cubense Tropical Race 4 (Foc TR4) infection. The expression of the tau class MaGSTs (MaGSTU1, MaGSTU2 and MaGSTU3) mainly responded to cold, salinity and drought while MaGSTF1 and MaGSTL1 expressions were upregulated by signaling molecules. Our findings suggest that MaGSTs play a key role in both development and abiotic stress responses.
    Matched MeSH terms: Glutathione Transferase/genetics
  7. Fulltext Insecticide resistance and resistance mechanisms in bed bugs, Cimex spp. (Hemiptera: Cimicidae)
    Dang K, Doggett SL, Veera Singham G, Lee CY
    Parasit Vectors, 2017 Jun 29;10(1):318.
    PMID: 28662724 DOI: 10.1186/s13071-017-2232-3
    The worldwide resurgence of bed bugs [both Cimex lectularius L. and Cimex hemipterus (F.)] over the past two decades is believed in large part to be due to the development of insecticide resistance. The transcriptomic and genomic studies since 2010, as well as morphological, biochemical and behavioral studies, have helped insecticide resistance research on bed bugs. Multiple resistance mechanisms, including penetration resistance through thickening or remodelling of the cuticle, metabolic resistance by increased activities of detoxification enzymes (e.g. cytochrome P450 monooxygenases and esterases), and knockdown resistance by kdr mutations, have been experimentally identified as conferring insecticide resistance in bed bugs. Other candidate resistance mechanisms, including behavioral resistance, some types of physiological resistance (e.g. increasing activities of esterases by point mutations, glutathione S-transferase, target site insensitivity including altered AChEs, GABA receptor insensitivity and altered nAChRs), symbiont-mediated resistance and other potential, yet undiscovered mechanisms may exist. This article reviews recent studies of resistance mechanisms and the genes governing insecticide resistance, potential candidate resistance mechanisms, and methods of monitoring insecticide resistance in bed bugs. This article provides an insight into the knowledge essential for the development of both insecticide resistance management (IRM) and integrated pest management (IPM) strategies for successful bed bug management.
    Matched MeSH terms: Glutathione Transferase/genetics*
  8. Fulltext GSTM1, GSTT1 and CYP1A1 polymorphisms and risk of oral cancer: a case-control study in Jakarta, Indonesia
    Amtha R, Ching CS, Zain R, Razak IA, Basuki B, Roeslan BO, et al.
    Asian Pac J Cancer Prev, 2009 Jan-Mar;10(1):21-6.
    PMID: 19469619
    PURPOSE: to investigate genetic polymorphisms in GSTM1, GSTT1 and CYP1A1 and the association with the risk of oral cancer in the Jakarta population.
    METHOD: A total of 81 cases and 162 controls matched for age and sex were selected from 5 hospitals in Jakarta. Sociodemographic data using questionnaires were obtained and peripheral blood samples were collected with informed consent for PCR-RFLP assay. Conditional logistic regression analysis was performed to obtain the association between the risk of oral cancer and GSTM1, GSTT1 and CYP1A1 polymorphisms.
    RESULTS: GSTM1 and GSTT1 null were slightly overrepresented among cases (60.5% and 45.7% respectively) compared to controls (55.6% and 41.4% respectively), but no statistically significant differences were observed. In contrast, the distribution of CYP1A1 polymorphism was higher among controls compared to cases (52.5 % versus 42.4 %). The odds ratio of null GSTM1 and GSTT1 genotypes was slightly higher compared to wild type genotypes (OR 1.19, 95% CI 0.70-2.02 and OR 1.19, 95% CI 0.72-2.05 respectively). Furthermore, the presence of CYP1A1 polymorphism did not increase the risk of oral cancer (OR 0.70, 95% 0.39-1.25).
    CONCLUSION: Genetic polymorphisms of GSTM1, GSTT1 and CYP1A1 may not be risk factors for oral cancer in the Jakarta population.
    Matched MeSH terms: Glutathione Transferase/genetics*
  9. The endothelial nitric oxide synthase gene G894T, glutathione S-transferase (GSTM1 and GSTT1) polymorphisms as a risk factor in the patient with nephrolithiasis
    Mehdi WA, Mehde AA, Yusof F, Raus RA, Resen AK, Ghazali H
    Int J Biol Macromol, 2019 Nov 01;140:719-726.
    PMID: 31445152 DOI: 10.1016/j.ijbiomac.2019.08.184
    BACKGROUND: The genetic features indicate a crucial role in nephrolithiasis. The present study was aimed to investigate the role of Glutathione-S-transferase Mu (GSTM1), Glutathione-S- transferase Theta (GSTT1) and endothelial nitric oxide synthase (eNOs) gene polymorphism in nephrolithiasis.

    METHODS: We involved a case-control study in which 480 individuals were divided into 240 healthy control and 240 patients with nephrolithiasis. For each patient and control, we measured biochemical criteria, levels of glutathione S-transferase, eNOs, GSTM1, GSTT1genes and eNOS genes polymorphism by PCR-RFLP.

    RESULTS: GSTM1 and GSTT1 null genotypes are not a risk features for nephrolithiasis. The eNOS frequency GG, GT, and TT genotypes by using Ban II enzyme as restriction enzyme were found to be (48.33, 36.67, and 15.00) %. The eNOS frequency TT, GT, and GG genotypes by using the Ban II enzyme as restriction enzyme were found to be 15.84, 25.83, and 58.33%, respectively. The result showed an increase in serum eNOs levels were in the patient's group comparing to control.

    CONCLUSIONS: This work is the first in the literature to study the relation between eNOs genes polymorphisms and nephrolithiasis. The results conclude that TT genotypes in the eNOs genes are associated with an increase the oxidative stress in patients.

    Matched MeSH terms: Glutathione Transferase/genetics*
  10. Characterization of Eleusine indica with gene mutation or amplification in EPSPS to glyphosate
    Chen J, Jiang C, Huang H, Wei S, Huang Z, Wang H, et al.
    Pestic Biochem Physiol, 2017 Nov;143:201-206.
    PMID: 29183593 DOI: 10.1016/j.pestbp.2017.09.012
    The evolution of weed-resistant species threatens the sustainable use of glyphosate, which is the most important herbicide widely used in agriculture worldwide. Moreover, the high glyphosate resistance (>180-fold based on LD50) of Eleusine indica found in Malaysia, which carries a double mutation in its 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), made the control of this species more difficult. By contrast, the same species carrying the same double mutation in EPSPS (T102I+P106S) but found in China only shows a resistance level of not more than 14-fold based on GR50. The resistance level of this population is four times higher than that of the population carrying a single mutation (P106L). Although the members of this population survive under a high glyphosate dosage of 10,080gaeha-1, their growth was significantly inhibited by glyphosate under the recommend dose (840gaeha-1), where in the fresh weight was 85.4% of the control. EPSPS expression, relative copy number, and EPSPS activity in this population were similar to those of the susceptible population. In addition, the expression of two glutathione transferase (GST) genes (GST-U8 and GST-23) and the enzyme activity of the GST in this population did not significantly differ from those of the susceptible population. This finding is important in elucidating the resistance of the naturally evolved glyphosate-resistant (GR) weed species carrying a double mutation in EPSPS to glyphosate.
    Matched MeSH terms: Glutathione Transferase/genetics
  11. Fulltext Enzymatic and molecular characterization of insecticide resistance mechanisms in field populations of Aedes aegypti from Selangor, Malaysia
    Leong CS, Vythilingam I, Liew JW, Wong ML, Wan-Yusoff WS, Lau YL
    Parasit Vectors, 2019 May 16;12(1):236.
    PMID: 31097010 DOI: 10.1186/s13071-019-3472-1
    BACKGROUND: Dengue is a serious public health problem worldwide, including in Selangor, Malaysia. Being an important vector of dengue virus, Aedes aegypti are subjected to control measures which rely heavily on the usage of insecticides. Evidently, insecticide resistance in Ae. aegypti, which arise from several different point mutations within the voltage-gated sodium channel genes, has been documented in many countries. Thus, this robust study was conducted in all nine districts of Selangor to understand the mechanisms of resistance to various insecticides in Ae. aegypti. Mosquitoes were collected from dengue epidemic and non-dengue outbreak areas in Selangor.

    METHODS: Using the Center for Disease Control and Prevention (CDC) bottle assays, the insecticide resistance status of nine different Ae. aegypti strains from Selangor was accessed. Synergism tests and biochemical assays were conducted to further understand the metabolic mechanisms of insecticide resistance. Polymerase chain reaction (PCR) amplification and sequencing of the IIP-IIS6 as well as IIIS4-IIIS6 regions of the sodium channel gene were performed to enable comparisons between susceptible and resistant mosquito strains. Additionally, genomic DNA was used for allele-specific PCR (AS-PCR) genotyping of the gene to detect the presence of F1534C, V1016G and S989P mutations.

    RESULTS: Adult female Ae. aegypti from various locations were susceptible to malathion and propoxur. However, they exhibited different levels of resistance against dichlorodiphenyltrichloroethane (DDT) and pyrethroids. The results of synergism tests and biochemical assays indicated that the mixed functions of oxidases and glutathione S-transferases contributed to the DDT and pyrethroid resistance observed in the present study. Besides detecting three single kdr mutations, namely F1534C, V1016G and S989P, co-occurrence of homozygous V1016G/S989P (double allele) and F1534C/V1016G/S989P (triple allele) mutations were also found in Ae. aegypti. As per the results, the three kdr mutations had positive correlations with the expressions of resistance to DDT and pyrethroids.

    CONCLUSIONS: In view of the above outcomes, it is important to seek new tools for vector management instead of merely relying on insecticides. If the latter must be used, regular monitoring of insecticide resistance should also be carried out at all dengue epidemic areas. Since the eggs of Ae. aegypti can be easily transferred from one location to another, it is probable that insecticide-resistant Ae. aegypti can be found at non-dengue outbreak sites as well.

    Matched MeSH terms: Glutathione Transferase/genetics
  12. Combined effects of isothiocyanate intake, glutathione S-transferase polymorphisms and risk habits for age of oral squamous cell carcinoma development
    Karen-Ng LP, Marhazlinda J, Rahman ZA, Yang YH, Jalil N, Cheong SC, et al.
    Asian Pac J Cancer Prev, 2011;12(5):1161-6.
    PMID: 21875259
    Dietary isothiocyanates (ITCs) found in cruciferous vegetables (Brassica spp.) has been reported to reduce cancer risk by inducing phase II conjugating enzymes, in particular glutathione S-transferases (GSTs). This case-control study was aimed at determining associations between dietary ITCs, GSTs polymorphisms and risk habits (cigarette smoking, alcohol drinking and betel-quid chewing) with oral cancer in 115 cases and 116 controls. Information on dietary ITC intake from cruciferous vegetables was collected via a semi-quantitative food frequency questionnaire (FFQ). Peripheral blood lymphocytes were obtained for genotyping of GSTM1, GSTT1 and GSTP1 using PCR multiplex and PCR-RFLP. Chi-square and logistic regression were performed to determine the association of ITC and GSTs polymorphism and risk of oral cancer. When dietary ITC was categorized into high (greater than/equal to median) and low (less than median) intake, there was no significant difference between cases and control group. Logistic regression yielding odd ratios resulted in no significant association between dietary ITC intake, GSTM1, GSTT1 or GSTP1 genotypes with oral cancer risk overall. However, GSTP1 wild-type genotype was associated with later disease onset in women above 55 years of age (p= 0.017). Among the men above 45 years of age, there was clinical significant difference of 17 years in the age of onset of oral cancer between GSTP1 wild-type + low ITC intake and GSTP1 polymorphism + high ITC intake (p= 0.001). Similar conditions were also seen among men above 45 years of age with risk habits like drinking and chewing as the earlier disease onset associated with GSTP1 polymorphism and high ITC intake (p< 0.001). This study suggests that combination effects between dietary ITCs, GSTP1 polymorphism and risk habits may be associated with the risk of oral cancer and modulate the age of disease onset.
    Matched MeSH terms: Glutathione Transferase/genetics*
  13. Copy number polymorphisms in new HapMap III and Singapore populations
    Ku CS, Teo SM, Naidoo N, Sim X, Teo YY, Pawitan Y, et al.
    J Hum Genet, 2011 Aug;56(8):552-60.
    PMID: 21677662 DOI: 10.1038/jhg.2011.54
    Copy number variations can be identified using newer genotyping arrays with higher single nucleotide polymorphisms (SNPs) density and copy number probes accompanied by newer algorithms. McCarroll et al. (2008) applied these to the HapMap II samples and identified 1316 copy number polymorphisms (CNPs). In our study, we applied the same approach to 859 samples from three Singapore populations and seven HapMap III populations. Approximately 50% of the 1291 autosomal CNPs were found to be polymorphic only in populations of non-African ancestry. Pairwise comparisons among the 10 populations showed substantial differences in the CNPs frequencies. Additionally, 698 CNPs showed significant differences with false discovery rate (FDR)<0.01 among the 10 populations and these loci overlap with known disease-associated or pharmacogenetic-related genes such as CFHR3 and CFHR1 (age related macular degeneration), GSTTI (metabolism of various carcinogenic compounds and cancers) and UGT2B17 (prostate cancer and graft-versus-host disease). The correlations between CNPs and genome-wide association studies-SNPs were investigated and several loci, which were previously unreported, that may potentially be implicated in complex diseases and traits were found; for example, childhood acute lymphoblastic leukaemia, age-related macular degeneration, breast cancer, response to antipsychotic treatment, rheumatoid arthritis and type-1 diabetes. Additionally, we also found 5014 novel copy number loci that have not been reported previously by McCarroll et al. (2008) in the 10 populations.
    Matched MeSH terms: Glutathione Transferase/genetics
  14. Glutathione S transferase-theta (GSTT1) genetic polymorphism among Chinese, Malays and Indians in Singapore
    Lee EJ, Wong JY, Yeoh PN, Gong NH
    Pharmacogenetics, 1995 Oct;5(5):332-4.
    PMID: 8563775
    Glutathione S-transferase-theta (GSTT1) is subject to a genetic polymorphism where approximately 50% of a Caucasian population are homozygous for the null allele. Because of the possible association of the polymorphism with increased cancer risk in individuals, we genotyped by polymerase chain reaction 187 normal Chinese, 167 normal Malays and 152 normal Indians from Singapore and Malaysia. The proportion of Chinese, Malays and Indians with the null genotype were 58%, 38% and 16% respectively and mirrored previously reported frequencies of the GSTM1 null genotype in these populations. The frequency of the combined GSTM1 and GSTT1 null genotypes among Chinese, Malays and Indians were 37%, 22% and 5% respectively. The similarity with predicted frequencies indicated no interaction between the two genetic polymorphisms.
    Matched MeSH terms: Glutathione Transferase/genetics*
  15. Frequency of mutant CYP1A1, NAT2 and GSTM1 alleles in normal Indians and Malays
    Zhao B, Lee EJ, Wong JY, Yeoh PN, Gong NH
    Pharmacogenetics, 1995 Oct;5(5):275-80.
    PMID: 8563767
    Several xenobiotic metabolizing enzymes, including CYP1A1, NAT2 and GSTM1, are subject to genetic polymorphisms. Because these enzymes are important for the detoxification and/or bioactivation of drugs and carcinogens, these polymorphisms have important implications in therapeutics and cancer susceptibility. The distributions of CYP1A1, NAT2 and GSTM1 genotype frequencies in unrelated individuals of the Indian (n = 139) and Malay (n = 146) populations were characterized by the polymerase chain reaction. The respective allelic frequencies of wild-type and mutant alleles of CYP1A1 were 0.82 and 0.18 for the Indians, and 0.69 and 0.31 for the Malays. The frequencies of wild-type, M1, M2 and M3 of NAT2 among Indians were 0.44, 0.20, 0.32 and 0.04 respectively. The corresponding NAT2 allelic frequencies in Malays were 0.41, 0.12, 0.38 and 0.09. The GSTM1*A allele could not be amplified in 33.1% of Indians and 61.6% of Malays. At least one GSTM1*B allele was detected in 7.2% and 7.5% of the respective populations. The allelic frequencies of CYP1A1, NAT2 and GSTM1 among Malays are similar to previously reported frequencies among Chinese in the region. These findings will be of importance in the determination of cancer risks in these populations.
    Matched MeSH terms: Glutathione Transferase/genetics*
  16. High level expression of thermostable lipase from Geobacillus sp. strain T1
    Leow TC, Rahman RN, Basri M, Salleh AB
    Biosci Biotechnol Biochem, 2004 Jan;68(1):96-103.
    PMID: 14745170
    A thermostable extracellular lipase of Geobacillus sp. strain T1 was cloned in a prokaryotic system. Sequence analysis revealed an open reading frame of 1,251 bp in length which codes for a polypeptide of 416 amino acid residues. The polypeptide was composed of a signal peptide (28 amino acids) and a mature protein of 388 amino acids. Instead of Gly, Ala was substituted as the first residue of the conserved pentapeptide Gly-X-Ser-X-Gly. Successful gene expression was obtained with pBAD, pRSET, pET, and pGEX as under the control of araBAD, T7, T7 lac, and tac promoters, respectively. Among them, pGEX had a specific activity of 30.19 Umg(-1) which corresponds to 2927.15 Ug(-1) of wet cells after optimization. The recombinant lipase had an optimum temperature and pH of 65 degrees C and pH 9, respectively. It was stable up to 65 degrees C at pH 7 and active over a wide pH range (pH 6-11). This study presents a rapid cloning and overexpression, aimed at improving the enzyme yield for successful industrial application.
    Matched MeSH terms: Glutathione Transferase/genetics
  17. Temporal proteomic profiling of Chlamydia trachomatis-infected HeLa-229 human cervical epithelial cells
    Tan GM, Lim HJ, Yeow TC, Movahed E, Looi CY, Gupta R, et al.
    Proteomics, 2016 05;16(9):1347-60.
    PMID: 27134121 DOI: 10.1002/pmic.201500219
    Chlamydia trachomatis is the leading causative agent of bacterial sexually transmitted infections worldwide which can lead to female pelvic inflammatory disease and infertility. A greater understanding of host response during chlamydial infection is essential to design intervention technique to reduce the increasing incidence rate of genital chlamydial infection. In this study, we investigated proteome changes in epithelial cells during C. trachomatis infection by using an isobaric tags for relative and absolute quantitation (iTRAQ) labeling technique coupled with a liquid chromatography-tandem mass spectrometry (LC-MS(3) ) analysis. C. trachomatis (serovar D, MOI 1)-infected HeLa-229 human cervical carcinoma epithelial cells (at 2, 4 and 8 h) showed profound modifications of proteome profile which involved 606 host proteins. MGST1, SUGP2 and ATXN10 were among the top in the list of the differentially upregulated protein. Through pathway analysis, we suggested the involvement of eukaryotic initiation factor 2 (eIF2) and mammalian target of rapamycin (mTOR) in host cells upon C. trachomatis infection. Network analysis underscored the participation of DNA repair mechanism during C. trachomatis infection. In summary, intense modifications of proteome profile in C. trachomatis-infected HeLa-229 cells indicate complex host-pathogen interactions at early phase of chlamydial infection.
    Matched MeSH terms: Glutathione Transferase/genetics
  18. In-silico analysis and mRNA modulation of detoxification enzymes GST delta and kappa against various biotic and abiotic oxidative stressors
    Chaurasia MK, Ravichandran G, Nizam F, Arasu MV, Al-Dhabi NA, Arshad A, et al.
    Fish Shellfish Immunol, 2016 Jul;54:353-63.
    PMID: 27109581 DOI: 10.1016/j.fsi.2016.04.031
    This study reports the comprehensive comparative information of two different detoxification enzymes such as glutathione S-transferases (GSTs) delta and kappa from freshwater giant prawn Macrobrachium rosenbergii (designated as MrGSTD and MrGSTK) by investigating their in-silico characters and mRNA modulation against various biotic and abiotic oxidative stressors. The physico-chemical properties of these cDNA and their polypeptide structure were analyzed using various bioinformatics program. The analysis indicated the variation in size of the polypeptides, presence or absence of domains and motifs and structure. Homology and phylogenetic analysis revealed that MrGSTD shared maximum identity (83%) with crustaceans GST delta, whereas MrGSTK fell in arthropods GST kappa. It is interesting to note that MrGSTD and MrGSTK shared only 21% identity; it indicated their structural difference. Structural analysis indicated that MrGSTD to be canonical dimer like shape and MrGSTK appeared to be butterfly dimer like shape, in spite of four β-sheets being conserved in both GSTs. Tissue specific gene expression analysis showed that both MrGSTD and MrGSTK are highly expressed in immune organs such as haemocyte and hepatopancreas, respectively. To understand the role of mRNA modulation of MrGSTD and MrGSTK, the prawns were inducted with oxidative stressors such as bacteria (Vibrio harveyi), virus [white spot syndrome virus (WSSV)] and heavy metal, cadmium (Cd). The analysis revealed an interesting fact that both MrGSTD and MrGSTK showed higher (P 
    Matched MeSH terms: Glutathione Transferase/genetics*
  19. Association of GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms with clinical response to imatinib mesylate treatment among Malaysian chronic myeloid leukaemia patients
    Makhtar SM, Husin A, Baba AA, Ankathil R
    J Genet, 2017 Sep;96(4):633-639.
    PMID: 28947711
    The detoxifying activity of glutathione S-transferases (GST) enzymes not only protect cells from the adverse effects of xenobiotics, but also alters the effectiveness of drugs in cancer cells, resulting in toxicity or drug resistance. In this study, we aimed to evaluate the association of GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms with treatment response among Malaysian chronic myeloid leukaemia (CML) patients who everyday undergo 400 mg of imatinib mesylate (IM) therapy. Multiplex polymerase chain reaction (multiplex-PCR) was performed to detect GSTM1 and GSTT1 polymorphisms simultaneously and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis was conducted to detect the GSTP1 Ile195Val polymorphism. On evaluating the association of the variant genotype with treatment outcome, heterozygous variant (AG) and homozygous variant (GG) of GSTP1 Ile105Val showed significantly a higher risk for the development of resistance to IM with OR: 1.951 (95% CI: 1.186-3.209, P = 0.009) and OR: 3.540 (95% CI: 1.305-9.606, P = 0.013), respectively. Likewise, GSTT1 null genotype was also associated with a significantly higher risk for the development of resistance to IM with OR = 1.664 (95% CI: 1.011-2.739, P = 0.045). Our results indicate the potential usefulness of GST polymorphism genotyping in predicting the IM treatment response among CML patients.
    Matched MeSH terms: Glutathione Transferase/genetics*
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