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Null Genotype (null + genotype)

Distribution by Scientific Domains
Medical Sciences78%
Life Sciences21%

Kinds of Null Genotype

  • gstm1 null genotype
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    Selected Abstracts

    Genetic and environmental interactions on oral cancer in Southern Thailand

    ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2001
    Suparp Kietthubthew
    Abstract Many countries are interested in understanding the relationship between genetic susceptibility and their prevalent environmental cancers for disease prevention. In Thailand we conducted a population-based case-control study of 53 matched pairs to assess the risk of oral cancer in relation to genetic polymorphism of the glutathione-S-transferase genes (GSTM1 and GSTT1) in cigarette smokers, alcohol drinkers, and betel quid chewers. Interaction of the genes with other potential risk factors such as local bean consumption were also elucidated. Homozygous deletion of GSTM1 has a frequency of 56.6% (n = 30 over 53) among the patients and 30.2% (16/53) among the controls. This gene is associated with a 2.6-fold higher risk for development of oral cancer (95% CI 1.04,6.5). Among the null GSTM1 individuals, those who smoke, consume alcohol, and/or chew betel quid have a significantly increased risk for oral cancer with an odd ratio (OR) = 4.0 (95% CI = 1.2,13.7), OR = 7.2 (95% CI = 1.5,33.8), and OR = 4.4 (95% CI = 1.1,17.8), respectively. Interactions between any two of the lifestyle habits for oral cancer risk, however, are not found. The frequency of the GSTT1 null genotype is 34.0% (18/53) among the patients and 47.2% (25/53) among our controls. There is no association between the GSTT1 null allele and oral cancer risk. In conclusion, our study provides data to indicate that individuals who have homozygous deletion of the GSTM1 gene have increased risk for oral cancer. The risk increases further when these individuals are exposed to environmental toxicants such as chemicals in cigarette smoke, alcohol, and betel quid. These baseline data can be applied to a larger population-based study, both to verify the observation and to conduct mechanistic investigations. Environ. Mol. Mutagen. 37:111,116, 2001 © 2001 Wiley-Liss, Inc. [source]

    Cytochrome P450 2D6 and glutathione S-transferase M1 genotypes and migraine

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2000
    Mattsson
    Background Migraine is thought to be a disease of the brain and trigeminovascular system. Migraine patients often claim that stress, food, and beverages trigger their attacks. Chemical substances in these foodstuffs with the property of triggering migraine attacks have not yet been characterised. Cytochrome P450 2D6 (CYP2D6) and glutathione S-transferase M1 (GSTM1) are thought to be present in the brain. They metabolise numerous environmental compounds. The genes exhibit genetic polymorphism that is associated with altered enzyme activity. The aim of this study was to determine if the genotypes of these two enzymes are associated with migraine. Materials and methods The study included 100 female patients and 245 female controls from the general population. Genomic DNA was isolated from whole blood. Allele specific PCR methods were used to identify the normal CYP2D6*1 allele and the mutated CYP2D6*3 and CYP2D6*4 alleles. Initially all samples were genotyped only for GSTM1 plus (+) and GSTM1 null (,) variants. All samples positive for GSTM1 were further analysed for the presence of allelic variants GSTM1*A and GSTM1*B. Results None of the CYP2D6 and GSTM1 genotypes was associated with migraine. We observed an odds ratio (OR) for the poor metaboliser genotype of CYP2D6 of 1.4 (95% CI = 0.5,3.6) and for the GSTM1 null genotype of 1.0 (95% CI = 0.6,1.5). Conclusion The results of this study indicate that deficient metabolism because of mutated CYP2D6 alleles or GSTM1 allele variants is not important in the aetiology of migraine. [source]

    Glutathione-S-transferase genotypes and the adverse effects of azathioprine in young patients with inflammatory bowel disease

    INFLAMMATORY BOWEL DISEASES, Issue 1 2007
    Gabriele Stocco PhD
    Abstract Background: Adverse drug reactions to azathioprine, the prodrug of 6-mercaptopurine, occur in 15%,38% of patients and the majority are not explained by thiopurine-S-methyltransferase (TPMT) deficiency. Azathioprine is known to induce glutathione depletion and consumption of glutathione is greater in cells with high glutathione-S-transferase (GST) activity compared with those with low activity; moreover, some reports indicate that GST might play a direct role in the reaction of glutathione with azathioprine. The association between polymorphisms of GST-M1, GST-P1, GST-T1, and TPMT genes and the adverse effects of azathioprine was therefore investigated. Methods: Seventy patients with inflammatory bowel disease (IBD), treated with azathioprine, were enrolled and clinical data were retrospectively determined. TPMT and GST genotyping were performed by polymerase chain reaction (PCR) assays on DNA extracted from blood samples. Results: Fifteen patients developed adverse effects (21.4%); there was a significant underrepresentation of the GST-M1 null genotype among patients developing adverse drug reactions to azathioprine (odds ratio [OR] = 0.18, 95% confidence interval [CI] = 0.037,0.72, P = 0.0072) compared with patients who did not develop adverse effects. Patients heterozygous for TPMT mutations presented a marginally significant increased probability of developing adverse effects (OR = 6.38, 95% CI = 0.66,84.1, P = 0.062). Moreover, among the 55 patients who did not develop adverse effects, there was a significant underrepresentation of the GST-M1 null genotype among patients who displayed lymphopenia as compared with those that did not display this effect of azathioprine (OR = 0.15, 95% CI = 0.013,1.08, P = 0.032). Conclusion: Patients with IBD with a wildtype GST-M1 genotype present increased probability of developing adverse effects and increased incidence of lymphopenia during azathioprine treatment. (Inflamm Bowel Dis 2007;13:57,64) [source]

    Glutathione S -transferase M3 (A/A) genotype as a risk factor for oral cancer and leukoplakia among Indian tobacco smokers

    INTERNATIONAL JOURNAL OF CANCER, Issue 1 2004
    Nilabja Sikdar
    Abstract Polymorphism in glutathione S -transferase (GST) genes, causing variations in enzyme activities, may influence susceptibility to oral cancer and leukoplakia in smokers and/or smokeless tobacco users. In this case-control study consisting of 109 leukoplakia and 256 oral cancer patients and 259 controls, genotype frequencies at GSTM1, GSTT1, GSTM3 and GSTP1 loci were determined by polymerase chain reaction-restriction fragment length polymorphism methods and analyzed by multiple logistic regression to determine the risks of the diseases. There were no significant differences in the distributions of GSTM1, GSTM3 and GSTT1 genotypes in patients and controls when all individuals were compared. In contrast, frequencies of ile/ile genotype at codon 105 and variant val-ala haplotype of GSTP1 was significantly higher (OR = 1.5; 95% CI = 1.0,2.0) and lower (OR = 1.4; 95% CI = 1.0,1.9) in oral cancer patients compare to controls, respectively. The impacts of all genotypes on risks of oral cancer and leukoplakia were also analyzed in patients with different tobacco habits and doses. Increased risks of cancer and leukoplakia were observed in tobacco smokers with GSTM3 (A/A) genotype (OR = 2.0, 95% CI = 1.0,4.0; OR = 2.0, 95% CI = 1.0,4.4, respectively). So, GSTM3 (A/A) genotype could become one of the markers to know which of the leukoplakia would be transformed into cancer. Heavy tobacco chewing (> 124 chewing-year) increased the risk of cancer in individuals with GSTT1 homozygous null genotype (OR = 3.0; 95% CI = 1.0,9.8). Furthermore, increased lifetime exposure to tobacco smoking (> 11.5 pack-year) increased the risk of leukoplakia in individuals with GSTM1 homozygous null genotype (OR = 2.4; 95% CI = 1.0,5.7). It may be suggested that polymorphisms in GSTP1, GSTM1, GSTM3 and GSTT1 genes regulate risk of cancer and leukoplakia differentially among different tobacco habituals. © 2003 Wiley-Liss, Inc. [source]

    GSTT1 and GSTM1 gene deletions are not associated with hepatotoxicity caused by antitubercular drugs

    JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2010
    S. Chatterjee MD
    Summary Background and objective:, Susceptibility to antitubercular drug (ATD)-induced hepatotoxicity may be genetically mediated, with variant alleles of genes such as N -acetyltransferase (NAT2) and CYP2E1 reported as risk factors. Two studies of Asian populations have reported that GSTM1*0/*0 (null) genotype was a likely predictor of hepatotoxicity, whereas another of a Caucasian population implicated GSTT1*0/*0. We undertook a prospective case,control study to investigate whether GSTM*0/*0 and GSTT1*0/*0 were risk factors for ATD-induced hepatotoxicity. Methods:, Pulmonary tuberculosis patients on isoniazid, rifampicin and pyrazinamide who developed hepatotoxicity using defined criteria were prospectively identified. These cases were then matched with at least one control subject on the same drugs but without hepatotoxicity. Genotyping for GSTM1 and GSTT1 was performed by multiplex PCR on genomic DNA. The odds ratios for the frequency of specific GSTM1 and GSTT1 homozygotes in the case and control subjects were calculated to test for association between the genotypes and hepatotoxicity. Results and discussion:, Hundred and fifty-one subjects (51 cases, 100 controls) were enrolled. Odds ratio for GSTM1 null genotype was 1·00 (95% CI 0·51,1·97) and GSTT1 null was 2·02 (95% CI 0·39,10·39), respectively, showing that these genotypes are not associated with hepatotoxicity. Conclusion:,GSTM1 *0/*0 or GSTT1 *0/*0 or both null genotypes, do not appear to be associated with ATD-induced hepatotoxicity in our Indian population. [source]

    Loss-of-function mutations and inducible RNAi suppression of Arabidopsis LCB2 genes reveal the critical role of sphingolipids in gametophytic and sporophytic cell viability

    THE PLANT JOURNAL, Issue 2 2008
    Charles R. Dietrich
    Summary Serine palmitoyltransferase (SPT) catalyzes the first step in sphingolipid biosynthesis, and downregulation of this enzyme provides a means for exploring sphingolipid function in cells. We have previously demonstrated that Arabidopsis SPT requires LCB1 and LCB2 subunits for activity, as is the case in other eukaryotes. In this study, we show that Arabidopsis has two genes (AtLCB2a and AtLCB2b) that encode functional isoforms of the LCB2 subunit. No alterations in sphingolipid content or growth were observed in T-DNA mutants for either gene, but homozygous double mutants were not recoverable, suggesting that these genes are functionally redundant. Reciprocal crosses conducted with Atlcb2a and Atlcb2b mutants indicated that lethality is associated primarily with the inability to transmit the lcb2 null genotype through the haploid pollen. Consistent with this, approximately 50% of the pollen obtained from plants homozygous for a mutation in one gene and heterozygous for a mutation in the second gene arrested during transition from uni-nucleate microspore to bicellular pollen. Ultrastructural analyses revealed that these pollen grains contained aberrant endomembranes and lacked an intine layer. To examine sphingolipid function in sporophytic cells, Arabidopsis lines were generated that allowed inducible RNAi silencing of AtLCB2b in an Atlcb2a mutant background. Studies conducted with these lines demonstrated that sphingolipids are essential throughout plant development, and that lethality resulting from LCB2 silencing in seedlings could be partially rescued by supplying exogenous long-chain bases. Overall, these studies provide insights into the genetic and biochemical properties of SPT and sphingolipid function in Arabidopsis. [source]

    Glutathione S-transferase M1, T1, and P1 polymorphisms and prostate cancer risk in middle-aged men

    THE PROSTATE, Issue 2 2006
    Ilir Agalliu
    Abstract BACKGROUND The glutathione S-transferase (GST) enzymes detoxify several carcinogens. Genetic polymorphisms in GSTM1, T1, and P1 (Ile105Val) have been associated with prostate cancer, however, results have been inconsistent across studies. METHODS Data from a population-based case-control study in King County, Washington, were used to further evaluate the relationships between these GST polymorphisms and prostate cancer. Incident cases (n,=,590) were 40,64 years old, diagnosed from 1993 through 1996, and identified via the SEER cancer registry. Controls (n,=,538) were identified via random digit dialing, and frequency age-matched to cases. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS Risk of prostate cancer was moderately increased among Caucasians with the GSTM1 -null genotype (OR,=,1.54; 95% CI 1.19,2.01). There were no associations for either GSTT1 or P1(Ile105Val). The association between the GSTM1 -null genotype and prostate cancer was not different according to cancer aggressiveness defined by stage at diagnosis and Gleason score. Among GSTM1 -null Caucasians, the relative risk of prostate cancer increased linearly with increasing pack-years of smoking (P -value for trend,=,0.007), with the highest ORs observed for smokers of >30 pack-years. CONCLUSIONS Findings suggest that the GSTM1 -null genotype defines a subgroup of men at higher risk of prostate cancer, particularly if they are heavy smokers. © 2005 Wiley-Liss, inc. [source]

    Role of glutathione S-transferase Mu-1 (GSTM1) polymorphism in oligospermic infertile males

    ANDROLOGIA, Issue 4 2010
    G. Tirumala Vani
    Summary The aim of this study was to examine whether an association exists between glutathione S-transferase Mu-1 (GSTM1) gene polymorphism and idiopathic male infertility. Forty-two men with infertility and 43 fertile men were recruited for this study. GSTM1 gene was analysed using PCR technique. The frequency of GSTM1 null (,) genotype was observed to be 45.2% in infertile men as against 20.09% in fertile men. Subjects with the GSTM1 null genotype had lower sperm concentrations and motility when compared with the subjects with GSTM1 -positive genotype in both the groups. This study shows that the frequency of GSTM1 null (,) genotype is significantly high in infertile males when compared with the frequency in fertile males (OR = 0.32, P = 0.017, 95% CI = 0.124,0.831). [source]

    Genetic polymorphisms and susceptibility to childhood acute lymphoblastic leukemia

    ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2 2004
    Renata Canalle
    Abstract Acute lymphoblastic leukemia (ALL) is the most common form of pediatric cancer. Although exposure to environmental agents appears to predispose individuals to this disease, little attention has been paid to the role of genetic susceptibility to environmental exposures in the etiology of childhood ALL. The enzymes GSTM1, GSTT1, GSTP1, CYP1A1, and CYP2E1 are involved in the bioactivation and detoxification of a variety of xenobiotics present in food, organic solvents, tobacco smoke, drugs, alcoholic drinks, pesticides, and environmental pollutants. Polymorphisms in the genes coding for these enzymes have been associated with increased susceptibility to different cancers, including hematologic malignancies. To investigate whether these polymorphisms represent risk-modifying factors for childhood ALL, a study was conducted involving 113 Brazilian patients of childhood ALL and 221 controls with similar ethnic backgrounds. The data revealed that carriers of the rare GSTP1 Val allele were at higher risk of ALL (odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.1,6.8; P = 0.04). No difference was found in the prevalence of the GSTM1 and GSTT1 null genotypes between ALL patients and the controls, and no association was found between CYP1A1*2 and CYP2E1*3 variants and ALL. However, when the mutant CYP1A1 and CYP2E1 alleles were considered together with the GSTM1 and GSTP1 risk-elevating genotypes, the risk of ALL was increased further (OR = 10.3; 95% CI = 1.0,111.8; P = 0.05), suggesting a combined effect. These results imply that genetic variants of xenobiotic metabolizing genes influence the risk of developing childhood ALL. Environ. Mol. Mutagen. 43:100,109, 2004. © 2004 Wiley-Liss, Inc. [source]

    GSTT1 and GSTM1 gene deletions are not associated with hepatotoxicity caused by antitubercular drugs

    JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2010
    S. Chatterjee MD
    Summary Background and objective:, Susceptibility to antitubercular drug (ATD)-induced hepatotoxicity may be genetically mediated, with variant alleles of genes such as N -acetyltransferase (NAT2) and CYP2E1 reported as risk factors. Two studies of Asian populations have reported that GSTM1*0/*0 (null) genotype was a likely predictor of hepatotoxicity, whereas another of a Caucasian population implicated GSTT1*0/*0. We undertook a prospective case,control study to investigate whether GSTM*0/*0 and GSTT1*0/*0 were risk factors for ATD-induced hepatotoxicity. Methods:, Pulmonary tuberculosis patients on isoniazid, rifampicin and pyrazinamide who developed hepatotoxicity using defined criteria were prospectively identified. These cases were then matched with at least one control subject on the same drugs but without hepatotoxicity. Genotyping for GSTM1 and GSTT1 was performed by multiplex PCR on genomic DNA. The odds ratios for the frequency of specific GSTM1 and GSTT1 homozygotes in the case and control subjects were calculated to test for association between the genotypes and hepatotoxicity. Results and discussion:, Hundred and fifty-one subjects (51 cases, 100 controls) were enrolled. Odds ratio for GSTM1 null genotype was 1·00 (95% CI 0·51,1·97) and GSTT1 null was 2·02 (95% CI 0·39,10·39), respectively, showing that these genotypes are not associated with hepatotoxicity. Conclusion:,GSTM1 *0/*0 or GSTT1 *0/*0 or both null genotypes, do not appear to be associated with ATD-induced hepatotoxicity in our Indian population. [source]

    Influence of glutathione- S -transferase theta (GSTT1) and mu (GSTM1) gene polymorphisms on the susceptibility of hepatocellular carcinoma in Taiwan,

    JOURNAL OF SURGICAL ONCOLOGY, Issue 4 2010
    Chia-Chun Kao MD
    Abstract Background and Objectives Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide and is the second leading cause of cancer death in Taiwan. Genetic polymorphism has been reported as a factor for increased susceptibility of HCC. Glutathione- S -transferases theta (GSTT1) and mu (GSTM1) play essential roles in detoxification of ingested xenobiotics and modulation of the susceptibility of gene-related cancer. The aim of this study was to estimate the relationships between these two gene polymorphisms and HCC risk and clinicopathological status in Taiwanese. Methods Polymerase chain reaction (PCR) was used to determine gene polymorphisms of 102 patients with HCC and 386 healthy controls. Results Both gene polymorphisms were not associated with the clinical pathological status of HCC and serum levels of liver-related clinical pathological markers. While no relationship between GSTM1 gene polymorphism and HCC susceptibility was found, individuals of age <56 years old with GSTT1 present genotype have a risk of 2.77-fold (95% CI: 1.09,7.09) for HCC compared to that with null variant, after adjustment for other confounders. Conclusions GSTT1 and GSTM1 null genotypes do not associate with increased risk of HCC. J. Surg. Oncol. 2010;102:301,307. © 2010 Wiley-Liss, Inc. [source]

    GSTM1 and GSTT1 null genotypes as possible heritable factors of rosacea

    PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 4 2006
    Ayca Cordan Yazici
    Purpose: Rosacea might be related to an increased activity of reactive oxygen species (ROS) and deficient function of the antioxidant system. Glutathione S-transferases (GSTs) play a primer role in cellular defense against electrophilic chemical species and radical oxygen species. We hypothesized that increased ROS activity or decreased antioxidant potential, possibly induced by GST gene polymorphism, might have a pathogenic role in rosacea. Methods: The study group consisted of 45 patients with rosacea and 100 control subjects. DNA samples were isolated from blood samples using high pure polymerase chain reaction (PCR) Template preparation Kit. The GSTM1, GSTT1, and P1 polymorphisms were detected using a real-time PCR and fluorescence resonance energy transfer with a Light-Cycler Instrument. Associations between specific genotypes and the development of rosacea were examined using logistic regression analyses to calculate odds ratios (OR) and 95% confidence intervals (CI). Results: GSTM1 and GSTT1 null genotypes were found to be statistically different from control (P=0.005, P=0.009, respectively), and associated with an increased risk of rosacea (OR [95% CI]: 2.84 [1.37,5.89]; OR [95% CI]: 2.68 [1.27,5.67], respectively). There was a statistically significant relationship between both null combination of the GSTM1 and GSTT1 genotype polymorphisms and rosacea (P=0.003, OR [95% CI]: 4.18 [1.57,11.13]). There were no statistically significant differences between patient and control groups for the GSTP1 Ile/Ile, Ile/Val, and Val/Val genotypes (P>0.05). Conclusion: We demonstrated a significant association between the GSTT1 and/or GSTM1 null genotypes and rosacea. However, the potential role of GSTs as markers of susceptibility to rosacea needs further studies in larger patient groups. [source]

    Genetic polymorphisms of glutathione S-transferase T1 (GSTT1) and susceptibility to gastric cancer: a meta-analysis

    CANCER SCIENCE, Issue 6 2006
    Mostafa Saadat
    The association between glutathione S-transferase T1 (GSTT1) polymorphism and gastric cancer risk has been both confirmed and refuted in a number of published studies. Most of these studies were based on small sample sizes. We carried out a meta-analysis of the research published up to August 2005 to obtain more precise estimates of gastric cancer risk associated with GSTT1 polymorphism. In the present study, 16 case-control studies (with a total of 6717 subjects) were eligible for meta-analysis. There was no evidence of heterogeneity between the studies. The GSTT1 null genotype conferred a 1.06-fold increased risk of gastric cancer, which was not significant (95% confidence interval [CI]: 0.94,1.19). However, in the analysis of ethnic groups, we observed distinct differences associated with GSTT1 status. Restricting analyses to ethnic groups, the pooled odd ratios for the GSTT1 genotype were 1.27 in Caucasians (95% CI: 1.03,1.57) and 0.98 in Asians (95% CI: 0.86,1.13). Glutathione S-transferase M1 (GSTM1) and GSTT1 are involved in detoxification of a variety of compounds, some that overlap between enzymes and some that are highly specific. To investigate whether the profile of glutathione S-transferase genotypes was associated with risk of gastric cancer, further analyses combining the GSTT1 and GSTM1 genotypes were also carried out. There was a significant trend in risk associated with zero, one and two putative high-risk genotypes (,2 = 9.326, d.f. = 1, P = 0.0023). Those who had null genotypes of GSTM1 and GSTT1 had an increased gastric cancer risk compared with those who had both active genes (odds ratio = 2.08, 95% CI: 1.42,3.10). (Cancer Sci 2006; 97: 505,509) [source]