• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5037-5042
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• 2012

Background: Tobacco contains agents which generate various potent DNA adducts that can cause gene mutations. Production of DNA adducts may be neutralized by glutathione S transferase (GST) along with other phase I and phase II enzyme systems. The existence of null type of GST among the population increases the susceptibility to various disorders and diseases. The present study focuses on the impact of high tobacco usage and possible null type mutation in GST loci. Methods: Genotypes of GST were detected by multiplex polymerase chain reaction in unrelated 504 volunteers of high tobacco using natives of Gujarat. Allelic frequencies were calculated using Statistical Package for Social Studies-16 software. Hardy Weinberg Equilibrium (HWE) was calculated using Chi square test. Two sided Fisher's significance test was used to compare allelic frequencies of different populations. Results: The frequency of homozygous null genotype of GSTM1 and GSTT1 were 20% (95% CI 16.7-23.9) and 35.5% (95% CI 31.4-39.9) respectively. The GSTM1 and GSTT1 null allele frequency distribution in the Gujarat population was significantly deviating from HWE. GSTT1 null frequency of Gujaratians was significantly higher and different to all reported low tobacco using Indian ethnics, while GSTM1 was not differing significantly. Conclusion: Tobacco usage significantly influences the rate of mutation and frequency of GSTT1 and M1 null types among the habituates. The rate of mutation in GSTT1 loci was an undeviating response to the dose of tobacco usage among the population. This mutational impact of tobacco on GSTT1 postulates the possible gene - environment interaction and selection of null genotype among the subjects to prone them under susceptible status for various cancers and even worst to cure the population with GSTT1 dependent drugs.

• Journal of Microbiology
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• v.39 no.2
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• pp.102-108
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• 2001

DNA damage response has a central role in the maintenance of genomic integrity while mutations in related genes may result in a range of disorders including neoplasic formations. The uvsZl characterized in this report is a navel uvs mutation in Aspergillus nidulans, resulting in a nucleotide excision repair (NER) phenotype: UV-sensitivity before DNA synthesis (quiescent cells), high UV-induced mutation frequency and probable absence of involvement with mitotic and meiotic recombinations. The mutation is recessive and nan-allelic to the previously characterized uvsA101 mutation, also located on the paba-y interval on chromosome I. uvsZl skewed wild-type sensitivity to MMS, which suggests non-involvement of this mutation with BER. Epitasis tests showed that the uvsZ gene product is probably involved in the same repair pathways as UVSB or UVSH proteins. Although mutations in these proteins result in an NER phenotype, UVSB is related with cell cycle control and UVSH is associated with the post-replicational repair pathway. The epistatic interaction among uvsZl and uvsB413 and uvsH77 mutations indicates that different repair systems may be related with the common steps of DNA damage response in Aspergillus nidulans.

• Journal of Genetic Medicine
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• v.1 no.1
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• pp.39-43
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• 1997

The mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is inherited maternally, in which the MTTL1*MELAS 3243 mutation has been most commonly found as a heteroplasmy of A to G point mutation in the $tRNA^{Leu(UUR)}$ gene. The MTTL1*MELAS 3271 mutation is known to be the second common mutation, though clinical features of both mutations are not remarkably different. Recently, a variety of minor mutations have been reported in patients with MELAS. In this study, major efforts have been made to investigate the allele frequency of major three mutations including MTTL1*MELAS 3243, 3252, 3271 in 10 Korean families with MELAS probands. The PCR and subsequent direct sequencing of the PCR product in the regions spanning these three mutation sites were employed to identify the mutation in each proband. All family members have been screened for the presence of these three mutations by PCR-RFLP assay using Apa I, Acc I and Bfr I restriction enzymes. The MTTL1*MELAS 3243 mutation was most commonly found (7 out of 10 families tested) followed by the MTTL1*MELAS 3271 which was identified in 1 out of 10 families. In the remaining 2 families none of three mutations were found, indicating the presence of either nuclear mutation or yet unidentified mitochondrial DNA mutation in these families.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.511-516
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• 2012

Background: We investigated the association between polymorphisms in the $p53$ tumor suppressor gene and breast cancer risk in women especially in the Southern part of India. Methods: Genotyping was performed for 50 breast cancer women and 50 controls to determine the status of $p53$ exon 4 codon 72 polymorphism and exon 7 codon 249 mutation and their possible role in breast cancer risk. Results: Frequency of Arg/Arg at codon 72 was 18% in controls and 28% in patients, Arg/Pro frequency was 56% and 66%, Pro/Pro genotype was 8% in controls and 8% in patients. No significance was observed for breast cancer risk with either Arg/Arg or Pro/Pro genotype in codon 72 polymorphism. Similarly, mutation analysis of exon 7 codon 249 revealed that 72% of breast cancer patients have mutation, which is not statistically significant. However, there is a strong association between increase in exon 7 codon 249 mutation and exposure to pollution. Conclusion: The results suggested that there is no risk for exon 4 with Arg/Arg or Pro/Pro polymorphisms in the $p53$ gene and there is no strong correlation between breast cancer patients and mutation in exon 7 codon 249 in South Indian women.

• Tuberculosis and Respiratory Diseases
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• v.80 no.3
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• pp.270-276
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• 2017

Background: A disputed rpoB mutation is a specific type of rpoB mutation that can cause low-level resistances to rifampin (RIF). Here, we aimed to assess the frequency and types of disputed rpoB mutations in Mycobacterium tuberculosis isolates from South Korea. Methods: Between August 2009 and December 2015, 130 patients exhibited RIF resistance on the MTBDRplus assay at Asan Medical Center. Among these cases, we identified the strains with disputed rpoB mutation by rpoB sequencing analysis, as well as among the M. tuberculosis strains from the International Tuberculosis Research Center (ITRC). Results: Among our cases, disputed rpoB mutations led to RIF resistance in at least 6.9% (9/130) of the strains that also exhibited RIF resistance on the MTBDRplus assay. Moreover, at the ITRC, sequencing of the rpoB gene of 170 strains with the rpoB mutation indicated that 23 strains (13.5%) had the disputed mutations. By combining the findings from the 32 strains from our center and the ITRC, we identified the type of disputed rpoB mutation as follows: CTG511CCG (L511P, n=8), GAC516TAC (D516Y, n=8), CTG533CCG (L533P, n=8), CAC526CTC (H526L, n=4), CAC526AAC (H526N, n=3), and ATG515GTG (M515V, n=1). Conclusion: Disputed rpoB mutations do not seem to be rare among the strains exhibiting RIF resistance in South Korea.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1053-1055
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• 2016

Background: Polycythemia rubra vera (PV), being a primary polycythemia, is caused by neoplastic proliferation of erythroid, megakaryocytic and granulocytic lineages which result in panmyelosis. PV patients have a somatic acquired mutation in the Janus kinase (JAK2) pathway, rendering cell proliferation independent of the normal regulatory mechanisms that regulate erythropoiesis. The rational of this study was to determine the prevalence of the JAK-2 V617F mutation in Pakistani patients with PV. Materials and Methods: In this cross sectional study, 26 patients with PV were enrolled from January 2010 to December 2014. Patients were diagnosed based on WHO criteria for PV. All were screened for G-T point mutation (V617F) in the JAK2 gene on chromosome 9 by an allele specific PCR. Results: The mean age was $53.4{\pm}9.31years$ (range 36-72) and the male to female ratio was 2:1. The frequency of JAK2 V617F positivity in our PV patients was found to be 92.3%. Overall 30.7% of patients were asymptomatic and remaining 69.3% presented with symptomatic disease. The mean hemoglobin was $18.1{\pm}1.9g/dl$ with the mean hematocrit of $55.6{\pm}8.3%$. The mean total leukocyte count was $12.8{\pm}7.1{\times}10^9/l$ and the platelet count was $511{\pm}341.9{\times}10^9/l$. A positive correlation of JAK2 V617F mutation was established with high TLC count (P=0.01). No correlation of JAK2 V617F could be established with age or gender (P>0.05). Conclusions: The JAK2 V617F mutation frequency in our PV patients was similar to those reported internationally. Screening for the mutation in all suspected PV cases could be beneficial in differentiating patients with reactive and clonal erythrocytosis.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.149-155
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• 2001

Eighty-one workers including 38 employees directly incinerating industry wastes were recruited from a company located in South Korea. To evaluate the association between urinary 1-hydroxypyrene glucuronide (1-OHPG) levels, as internal dose of polycyclic aromatic hydrocarbon (PAH) exposure, and glycophorin A (GPA) mutation frequency, as an early biologic effect indicator. Urinary 1-OHPG levels were measured by synchronous fluorescence spectroscopy after immunoaffinity purification using monoclonal antibody 8E11. Erythrocyte GPA variant frequency (NN or NO) was assessed in MN heterozygotes with a flow cytometic assay. The GSTM1 and GSTT1 genotypes were assessed by a multiplex PCR method. The GPA NN phenotype frequency was higher in occupationally exposed group (n=14, mean$\pm$S.D. 6.6$\pm$12.0 in 10/SUP 6/ erythrocyte cells) than in non-exposed group (n=22, 2.1$\pm$3.5). Similarly, the GPA(NO or NN) phenotype frequency was higher in exposed group (n=14, 9.7$\pm$17.3) than non-exposed group (n=22, 4.2$\pm$6.3). The above differences failed to reach statistical significance, but a significant increase was seen in GPA variant frequency levels with increase in urinary 1-OHPG levels (Spearman's correlation: p=0.06 (NO), p=0.07 (NO or NN)). When this association was evaluated by GSTM1 genotype status, the association between GPA mutation and urinary 1-OHPG levels was stronger in individuals with GSTM1 present genotype (Spearmans correlation; r=0.50, p=0.02). These results suggest that the association between urinary 1-OHPG and GPA mutation is be modulated by the GSTM1 genotype.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7327-7330
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• 2015

Background: Essential thrombocythemia (ET) is a clonal hemopoietic stem cell myeloproliferative neoplasm characterized by persistent thrombocytosis along with megakaryocytic hyperplasia. In the last decade following the identification of an acquired JAK2 V617F mutation, there has been acceleration in our understanding of this disease. The rational of this study was to determine the mutational profile of JAK2 V617F in Pakistan patients with ET. Materials and Methods: In this retrospective cross sectional study, 21 patients with ET were enrolled from January 2011 to December 2014. Patients were diagnosed based on WHO criteria for essential thrombocythemia. Complete blood count was done on an automated hematology analyzer, while JAK2 V617F expression was evaluated by polymerase chain reaction. Results: The mean age was $56.7{\pm}19.0$ years (range 18-87) and the male to female ratio was 1:1.1. The frequency of JAK2 V617F positivity in our ET patients was found to be 61.9%. The mean hemoglobin was $11.7{\pm}2.4$ g/dl with a total leukocyte count of $13.3{\pm}8.1{\times}109/l$ and a platelet count of $1188{\pm}522{\times}109/l$. Positive correlations for JAK2 V617F mutation were established with high TLC count and raised LDH (P<0.05). No correlation of JAK2 V617F could be established with age and gender (P>0.05). Conclusions: JAK2 V617F mutation frequency in our ET patients was similar to those reported previously. Screening for the mutation in all suspected essential thrombocythemia cases could be beneficial in differentiating patients with reactive and clonal thrombocytosis.

• Journal of Microbiology and Biotechnology
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• v.23 no.9
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• pp.1293-1303
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• 2013

Antibiotic resistance of soilborne Acinetobacter species has been poorly explored. In this study, norfloxacin resistance of a soil bacterium, Acinetobacter oleivorans DR1, was investigated. The frequencies of mutant appearance of all tested non-pathogenic Acinetobacter strains were lower than those of pathogenic strains under minimum inhibitory concentration (MIC). When the quinolone-resistance-determining region of the gyrA gene was examined, only one mutant (His78Asn) out of 10 resistant variants had a mutation. Whole transcriptome analysis using a RNA-Seq demonstrated that genes involved in SOS response and DNA repair were significantly up-regulated by norfloxacin. Determining the MICs of survival cells after norfloxacin treatment confirmed some of those cells were indeed persister cells. Ten colonies, randomly selected from among those that survived in the presence of norfloxacin, did not exhibit increased MIC. Thus, both the low mutation frequency of the target gene and SOS response under norfloxacin suggested that persister formation might contribute to the resistance of DR1 against norfloxacin. The persister frequency increased without a change in MIC when stationary phase cells, low growth rates conditions, and growth-deficient dnaJ mutant were used. Taken together, our comprehensive approach, which included mutational analysis of the target gene, persister formation assays, and RNA sequencing, indicated that DR1 survival when exposed to norfloxacin is related not only to target gene mutation but also to persister formation, possibly through up-regulation of the SOS response and DNA repair genes.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7889-7892
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• 2015

Background: Primary idiopathic myelofibrosis (PMF) is a clonal Ph-chromosome negative myeloproliferative neoplasm characterized by dysregulated kinase signaling and release of abnormal cytokines. In the recent past, following JAK2 V617F mutation invention, important revolution has been made in the molecular diagnostic biology of this disease. The rational of this study was to determine the mutational status of JAK2 V617F in Pakistan patients with PMF. Materials and Methods: In this cross sectional study, 20 patients with PMF were enrolled from January 2011 to December 2014. Diagnosis was based on WHO criteria for PMF. All patients were screened for G-T point mutation (V617F) in the JAK2 gene on chromosome 9 by allele specific PCR. Results: The mean age was $57.9{\pm}16.5years$. The male to female ratio was 3:1. The frequency of JAK2 V617F positivity in our PMF patients was found to be 55%. Positive correlations of JAK2 V617F mutation were established with high TLC count, raised LDH and marked splenomegaly (P<0.05). No correlation of JAK2 V617F could be established with age and gender (P>0.05). Conclusions: The JAK2 V617F mutation frequency in our PMF patients was similar to those reported previously. In our hands JAK2 V617F mutated patients expressed an aggressive disease phenotype. Screening for the mutation in all suspected PMF cases could be beneficial in differentiating patients with reactive and clonal marrow fibrosis.