The functional assay identified authentic interactions between CAPA peptides and the CAPA receptor isoforms in Bemisia tabaci (Gennadius).

CAPA neuropeptides regulate the diuresis/ antidiuresis process in insects by activating specific cognate receptor, CAPAr. In this study, we characterized the CAPAr gene (BtabCAPAr) in the whitefly, Bemisia tabaci Asia II 1. The two alternatively spliced isoforms of BtabCAPAr gene, BtabCAPAr-1 and BtabCAPAr-2, having six and five exons, respectively, were identified. The BtabCAPAr gene expression was highest in adult whitefly as compared to gene expression in egg, nymphal and pupal stages. Among the three putative CAPA peptides, CAPA-PVK1 and CAPA-PVK2 strongly activated the BtabCAPAr-1 with very low EC50 values of 0.067 nM and 0.053 nM, respectively, in heterologous calcium mobilization assays. None of the peptide activated the alternatively spliced isoform BtabCAPAr-2 that has lost the transmembrane segments 3 and 4. Significant levels of mortality were observed when whiteflies were fed with CAPA-PVK1 at 1.0 µM (50.0%), CAPA-PVK2 at 100.0 nM (43.8%) and CAPA-tryptoPK 1.0 µM (40.0%) at the 96 h after the treatment. This study provides valuable information to design biostable peptides to develop a class of insecticides.

Knockout of ecdysis triggering hormone receptor (ETHr) gene adversely affects the nymphal molting and adult reproduction in Bemisia tabaci.

Bemisia tabaci (Gennadius) is one of the most dangerous polyphagous pests in the world causing damage to various crops by sucking sap during the nymphal and adult stages. Chemical management of whiteflies is challenging because of the emergence of pesticide resistance. RNA interference has been well established in whitefly to study the functions of various genes. G-protein coupled receptors (GPCRs) are important targets for development of new generation insecticides. In this study, Ecdysis triggering hormone receptor (ETHr) gene expression was recorded in different stages of whitefly and its function has been studied through RNAi. The expression of ETHr is highest in third-instar nymphs followed by other nymphal instars, pupae and newly emerged adults. Silencing of ETHr resulted in significantly higher adult mortality (68.88%), reduced fecundity (4.46 eggs /female), reduced longevity of male and female (1.05 and 1.40 days, respectively) when adults were fed with dsETHr @ 1.0 µg/µl. Silencing of ETHr in nymphs lead to significantly higher mortality (81.35%) as compared to control. This study confirms that ETHr gene is essential for growth and development of whitefly nymphs and adults. Hence, it can be future target for developing dsRNA based insecticides for management of whitefly.

Bee-safe peptidomimetic acaricides achieved by comparative genomics.

The devastating Varroa mite (Varroa destructor Anderson and Trueman) is an obligatory ectoparasite of the honey bee, contributing to significant colony losses in North America and throughout the world. The limited number of conventional acaricides to reduce Varroa mites and prevent disease in honey bee colonies is challenged with wide-spread resistance and low target-site selectivity. Here, we propose a biorational approach using comparative genomics for the development of honey bee-safe and selective acaricides targeting the Varroa mite-specific neuropeptidergic system regulated by proctolin, which is lacking in the honey bee. Proctolin is a highly conserved pentapeptide RYLPT (Arg-Tyr-Leu-Pro-Thr) known to act through a G protein-coupled receptor to elicit myotropic activity in arthropod species. A total of 33 different peptidomimetic and peptide variants were tested on the Varroa mite proctolin receptor. Ligand docking model and mutagenesis studies revealed the importance of the core aromatic residue Tyr2 in the proctolin ligand. Peptidomimetics were observed to have significant oral toxicity leading to the paralysis and death of Varroa mites, while there were no negative effects observed for honey bees. We have demonstrated that a taxon-specific physiological target identified by advanced genomics information offers an opportunity to develop Varroa mite-selective acaricides, hence, expedited translational processes.

Clinical Utility of Transient Elastography in the Management of Patients with Budd-Chiari Syndrome Undergoing Endovascular Intervention.

PURPOSE: To quantify liver stiffness measurement (LSM) changes after endovascular intervention for Budd-Chiari syndrome (BCS) and evaluate whether LSM changes predict restenosis after endovascular intervention. MATERIALS AND METHODS: Patients with BCS who underwent endovascular intervention and had at least 2 LSM values available after the intervention were included. ΔLSM was the difference between LSMs estimated at the last and second last hospital visits. In patients with restenosis, 2 LSM values before restenosis were included. ΔLSM% was calculated as the ratio of ΔLSM to the LSM at the second last visit and expressed as a percentage. Odds ratio (OR) with confidence interval (CI) and area under the receiver operating characteristic curves (AUROCs) were calculated for the predictors of restenosis. RESULTS: The median baseline and postinterventional 1-week, 3-month, 6-month, and 12-month LSM values were 47.2 kPa (33.8-68.4 kPa), 29.2 kPa (24.5-43.0 kPa), 26.2 kPa (18.6-38.9 kPa), 20.9 kPa (13.3-29.8 kPa), and 17.3 kPa (11.8-25.4 kPa), respectively. Of the 118 patients, including 67 men, restenosis developed in 10 patients after a median (interquartile range) duration of 19 months (11-46 months). ΔLSM% was higher (more positive) in patients with restenosis than in those without restenosis (44.7 [8.3-134.3] vs -6.6 [-19.4 to 14.9], P = .001). ΔLSM% was a significant predictor of restenosis with an OR of 1.032 (95% CI, 1.015-1.050; P < .001). The AUROC for ΔLSM% was 0.831 (95% CI, 0.750-0.893; P = .001), and a ΔLSM% increment of 13.2% predicted restenosis with a sensitivity and specificity of 80.0% and 74.1%, respectively. CONCLUSIONS: LSM gradually decreases after endovascular intervention, and transient elastography is a promising test for detecting restenosis after the endovascular treatment of patients with BCS.

Impact of Corona Virus Disease 2019 pandemic on adherence to gluten-free diet in Indian patients with celiac disease.

AIMS: Lockdown and restricted mobility due to the pandemic of corona virus disease  2019 (COVID-19) has severely affected the continuity of healthcare of patients with acute and chronic diseases. We evaluated the impact of COVID-19 on the adherence to gluten-free diet (GFD), symptom control, and quality of life (QOL) in patients with celiac disease (CeD). METHODS: A questionnaire, consisting of both ad-hoc and validated questions, was created after review of literature, group discussions, and expert meetings. Standardized questionnaires namely CeD adherence test (CDAT), celiac symptom index score, and CeD-related QOL were used. The web-based questionnaire was sent to 3130 patients via social media and 452 responses (14.4%) were received. Also, additional 68 patients (not available on any social media application) were interviewed telephonically by a trained dietitian. RESULTS: Overall, 505 patients (females: 318; mean age: 24.1±14.2 years) were included. While only 6.7% (n = 34) had poor compliance to GFD (CDAT > 17) before COVID-19 pandemic, it almost doubled to 12.6% (n = 64) during the COVID-19 pandemic times (p = 0.02). Furthermore, 4.9% (n = 25) of patients were diagnosed contacting  COVID-19. Interestingly, 73.2% (n = 370) patients preferred online appointment than physical appointment. Most common difficulties faced during lockdown period were high delivery charges for getting gluten-free (GF) food at home (54.4%), increased prices of regular GF food (43.1%), and travelling long distance to arrange GF food (44.9%). CONCLUSIONS: The COVID-19 pandemic has substantially affected the adherence, symptom control, and QOL in patients with CeD, attributable to unavailability, shortage of money, and heightened cost of GF food. The pandemic has offered an opportunity to practice teleconsultation approach for patients with CeD.

Physico-chemical characterization of kajjali, black sulphide of mercury, with respect to the role of sulfur in its formation and structure.

BACKGROUND: Kajjali is used as a base for Ayurvedic herbo-mineral medicines. It is a combination of mercury with sulfur in varying proportions. The ratio of sulfur (S) added to mercury (Hg) directly relates to the therapeutic efficacy of the compound. OBJECTIVE: To analyze the physico-chemical characteristics of samaguna gandhaka kajjali (Hg: S = 1:1) and shadaguna gandhaka kajjali (Hg: S = 1:6). MATERIALS AND METHODS: X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy (XPS), Fourier transmission infrared spectroscopy, thermo-gravimetry analysis, and atomic absorption spectroscopy were applied to characterize each type of kajjali. RESULTS: It was found that the particle size of the formed kajjali compound increases with a decrease in the mercury to sulfur ratio. The presence of excess sulfur does not change the surface oxidation states as revealed by the XPS analysis. No trace of mercury has been found in both samaguna gandhaka kajjali (SGK-1) and shadguna gandhaka kajjali (SGK-6), indicating a complete Hg reaction with S. CONCLUSION: Kajjali simulates nanomaterial of the modern era and possesses therapeutic efficacy as mentioned in classical Ayurveda texts. Complete trituration of mercury and sulfur combination ends up with this kajjali formation incorporating the potency of nanotherapeutics.

Functional Characterization of Ecdysis Triggering Hormone Receptors (AgETHR-A and AgETHR-B) in the African Malaria Mosquito, Anopheles gambiae.

Insect ecdysis behavior, shedding off the old cuticle, is under the control of specific neuropeptides with the top command by the ecdysis triggering hormone (ETH). We characterized the ETH receptor (ETHR) of the malaria mosquito, Anopheles gambiae, by manual annotation of the NCBI gene (AGAP002881) and functional analysis, using a heterologous expression system in a mammalian cell line. The two splicing variants of ETHRs, ecdysis triggering hormone receptors (AgETHR-A and AgETHR-B), a conserved feature among insects, included of four (552 aa) and five exons (635 aa), respectively. The main feature of manual annotation of the receptor was a correction of N-terminal and exon-intron boundaries of an annotated gene (AGAP002881). Interestingly, the functional expression of the receptor in Chinese hamster ovary cells required modification of the transcription initiation site for mammalian Kozak consensus. In the calcium mobilization assay using the heterologous expression of each receptor, AgETHR-B showed a higher sensitivity to AgETH-1 (28 times) and AgETH-2 (320 times) than AgETHR-A. The AgETHRs showed specificity only to the ETH group of peptides but not to other groups carrying the C-termini motifs as PRXamide, such as pyrokinin1/DH and pyrokinin2/PBAN. Ecdysis triggering hormone receptors (AgETHR-B) responded to different ETH variants of other insect species more promiscuously than AgETHR-A.

Target of rapamycin (TOR) gene is vital for whitefly survival and reproduction.

The whitefly Bemisia tabaci (Gennadius) is a devastating polyphagous pest that causes significant losses in several economically important crops worldwide. Although chemical control is the fastest management strategy, insecticide resistance development poses a greater constraint in whitefly management. In this study, we used RNA interference (RNAi) technique to understand the role of target of rapamycin (TOR) gene in whitefly. In insects, TOR plays a crucial role in cell growth, metabolism, proliferation, and reproduction. Although sequence analyses of TOR revealed 95 nucleotides different in TOR gene sequence compared to predicted sequence (GenBank accession no. XM019060193.1), but this led to synthesis of only two different amino acids at positions 1448 and 1768. Phylogenetic analysis of amino acid sequence revealed that TOR gene of B. tabaci, Acrythosiphum pisum and Nilaparvata lugens were more closely related to each other and were clustered together. Oral feeding of artificial diet containing dsRNA viz 2.0, 1.0, 0.5, 0.1 µg/µl corresponding to TOR gene to adult whitefly resulted in 42.5% adult mortality, reduced fecundity i.e. 36.57 eggs per female, and 62.50% total nymphal mortality in the next generation. The qRT-PCR analysis confirmed the downregulation of TOR gene expression in adult whiteflies upon dstor feeding. These results suggest that TOR gene significantly regulates the survival and reproduction in whitefly and can be a potential RNAi target for insect management.

FibroScan-aspartate aminotransferase score in an Asian cohort of non-alcoholic fatty liver disease and its utility in predicting histological resolution with bariatric surgery.

BACKGROUND AND AIM: The FibroScan-aspartate aminotransferase (FAST) score was developed for identifying patients with non-alcoholic steatohepatitis, who also have an elevated non-alcoholic fatty liver disease (NAFLD) activity score (NAS) ≥ 4 and significant fibrosis (F ≥ 2). We aimed to validate it in our NAFLD cohort and assess if it correlates with the histological changes after bariatric surgery. METHODS: Patients with NAFLD, including those undergoing bariatric surgery, were included. The FAST score was calculated using liver stiffness measure, controlled attenuation parameter, and aspartate aminotransferase. Calibration and discrimination of the model were assessed by calibration plots and area under the receiver operating characteristic curve, respectively. Sensitivity and specificity were assessed at the rule-out and rule-in cutoffs (≤0.35 and ≥0.67), respectively. Changes in the NAS and FAST scores were compared in the bariatric cohort 1 year after surgery. RESULTS: The cohort composed of 309 patients, of which 48 patients underwent repeat liver biopsy at 1 year. The model showed good discrimination with area under the receiver operating characteristic curve of 0.79 (0.74-0.84); however, it was not satisfactorily calibrated (Hosmer-Lemeshow test, P = 0.008). The sensitivity and specificity at the rule-out and rule-in cutoffs were 0.90 and 0.84, respectively. A significant correlation was seen between the 1-year reduction in the NAS and FAST scores (r = 0.38, P = 0.009). A significant reduction in the median FAST score was seen in patients who had ≥2-point reduction in NAS after bariatric surgery. CONCLUSION: FibroScan-aspartate aminotransferase score demonstrated good discrimination for fibrotic non-alcoholic steatohepatitis in our cohort. However, a miscalibration resulted in overprediction. The score correlated well with the histological response to interventions for NAFLD.

Potential of RNA interference in the study and management of the whitefly, Bemisia tabaci.

Whiteflies cause considerable losses to crops, directly by feeding, and indirectly by transmission of viruses. The current control methods consist of a combination of different control tactics, mainly still relying on unsafe and non-ecofriendly chemical control. RNA interference (RNAi) is a post-transcriptional gene-silencing strategy in which double-stranded RNA (dsRNA), corresponding specifically to a target gene, is introduced in a target organism. Research on RNAi in the previous decade has shown its success as a potential insect control strategy, which can be highly species-specific and environment friendly. In whiteflies, the success of dsRNA delivery through the oral route opened possibilities for its management through plant-mediated RNAi. To date, several genes have been targeted in whiteflies through RNAi and these assays demonstrated its potential to manage whiteflies at lab level. However, further research and investments are needed to move toward an application at field level. In this review, for the first time, we collected the literature on genes targeted for silencing via RNAi in whiteflies and discuss the potential of RNAi in whitefly pest control. We also discuss likely delivery methods, including transgenic in planta delivery and symbiont-mediated delivery, and its potential for studying and interfering with insecticide resistance mechanisms and virus transmission by whiteflies.

Comparative evaluation of manual scaling and root planing with or without magnification loupes using scanning electron microscope: A pilot study.

AIM: The aim of the present study is to compare the amount of remaining calculus, loss of tooth substance, and roughness of root surface after scaling and root planing with or without magnification loupes using scanning electron microscope. MATERIALS AND METHODS: In the study, 30 teeth indicated for extractions due to severe chronic generalized periodontitis were included in the study. In test Group I, scaling and root planing was performed without magnification loupes, and in test Group II, scaling and root planing was performed with magnification loupes before extraction. In control Group III, no procedure was performed. After scaling and root planing, teeth were extracted followed by preparation of specimens. Specimens were then sent for scanning electron microscope study. RESULTS: Statistically significant (P ≤ 0.05) differences were found among different test groups. Results showed that test Group II with magnification loupes had less remaining calculus and smoother surface with lesser amount of loss of cementum layer. CONCLUSION: From this, it was concluded that test Group II was more efficient in root debridement than test Group 1, so scaling and root planing done with magnification loupes will cause less damage to the tooth surface.

Bioremediation of organophosphorus pesticide phorate in soil by microbial consortia.

Microbial consortia isolated from aged phorate contaminated soil were used to degrade phorate. The consortia of three microorganisms (Brevibacterium frigoritolerans, Bacillus aerophilus and Pseudomonas fulva) could degrade phorate, and the highest phorate removal (between 97.65 and 98.31%) was found in soils inoculated with mixed cultures of all the three bacterial species. However, the mixed activity of any of two of these bacteria was lower than mixed consortia of all the three bacterial species. The highest degradation by individual mixed consortia of (B. frigoritolerans+B.aerophilus, B. aerophilus+P. fulva and B. frigoritolerans+P. fulva) appeared in soil between (92.28-94.09%, 95.45-97.15% and 94.08-97.42%, respectively). Therefore, inoculation of highly potential microbial consortia isolated from in situ contaminated soil could result in most effective bioremediation consortia for significantly relieving soils from phorate residues. This much high phorate remediation from phorate contaminated soils have never been reported earlier by mixed culture of native soil bacterial isolates.

Studies on bromadiolone resistance in Rattus rattus populations from Punjab, India.

There are several reports on development of resistance to bromadiolone in different species of rodents around the globe, however, there is no such report involving systematic study from India. Hence, present study was carried out to investigate current status of bromadiolone resistance in house rat (Rattus rattus; n=154) collected from different poultry farms (n=8) based on feeding test, blood clotting response (BCR) test and molecular characterization of VKORC1 gene. Based on feeding test and BCR test, 28% rats were suspected to be resistant. Molecular analysis of VKORC1 gene of four suspected to be resistant rats having Prothrombin Time (PT) <70s, International Normalized Ratio (INR) <4.0 and died between 26 and 73days after treatment revealed no single nucleotide polymorphism (SNP) in nucleotide sequences. None of the sample under study showed complete nucleotide homology with previously reported nucleotide sequences of R. rattus. The sequences of VKORC1 gene under study can thus be considered as the novel sequences. Present investigation on molecular characterization of VKORC1 gene did not reveal any genetic resistance in Rattus rattus population against bromadiolone though rats could be considered resistant based on BCR and feeding tests.

Variations in the frenal morphology in the diverse population: A clinical study.

BACKGROUND: The upper labial frenum is a normal anatomic structure with inherent morphological variations. Frenum has variations depending upon the attachment of fibers along with the presence of structural variations. AIM: The aim of this study was to evaluate the prevalence of frenal variations in a diverse ethnic population of Sundernagar, Himachal Pradesh. MATERIALS AND METHODS: This study was conducted on 500 subjects within age group of 16-40 years (285 females, 215 males). Intraoral examination was done to evaluate the variations in frenum and photographs were taken. RESULTS: In this study, depending upon structural variations, normal frenum was most common followed by frenum with nodule while frenum with appendix was found to be least common. However, no significant difference was found between males and females (P > 0.05) with respect to all frenal attachments. Furthermore, other structural variations were found in the diverse population of Sundernagar, Himachal Pradesh. CONCLUSION: Upper labial frenum is a small anatomical landmark in the oral cavity found to have diverse morphology. The dentist needs to give due importance for frenum assessment during the oral examination.

Molecular phylogenetic analysis of mango mealybug, Drosicha mangiferae from Punjab.

Mealybugs (Hemiptera: Pseudococcidae) are major pests of a wide range of crops and ornamental plants worldwide. Their high degree of morphological similarity makes them difficult to identify and limits their study and management. In the present study, four Indian populations of mango mealybug (mango, litchi, guava from Gurdaspur and mango from Jalandhar) were analyzed. The mtCOI region was amplified, cloned, the nucleotide sequences were determined and analysed. All the four species were found to be D. mangiferae. The population from Litchi and Mango from Gurdaspur showed 100% homologus sequence. The population of Guava-Gurdaspur and Mango-Jalandhar showed a single mutation of 'C' instead of 'T' at 18th and 196th position, respectively. Indian populations were compared with populations from Pakistan (21) and Japan (1). The phylogenetic tree resulted in two main clusters. Cluster1 represent all the 4 populations of Punjab, India, 20 of Pakistan (Punjab, Sind, Lahore, Multan, Faisalabad and Karak districts) with homologous sequences. The two population collected from Faisalabad district of Pakistan and Japan made a separate cluster 2 because the gene sequence used in analysis was from the COI-3p region. However, all the other sequence of D. mangiferae samples under study showed a low nucleotide divergence. The homologus mtCO1 sequence of Indian and Pakistan population concluded that the genetic diversity in mealybug population was quite less over a large geographical area.

Optimization of growth conditions and medium composition for improved conidiation of newly isolated Beauveria bassiana strains.

Beauveria bassiana is an entomopathogenic fungus with high potential in controlling insect pests. In this study, we propose optimum cultural conditions and culture media for better growth of various B. bassiana strains. B. bassiana strains achieved their maximum growth during optimal incubation period of seven days. The optimum pH and temperature for maximal growth of B. bassiana strains was found to be 6-7 and 25-30°C, respectively. All the tested carbon and nitrogen sources supported growth and development of the B. bassiana strains. Starch and peptone as carbon and nitrogen sources supported maximum radial growth (2.13-3.00 cm) and conidiospore count in both solid state culture (2.66x107 conidia/mL) and liquid state culture (9.86x107 conidia/mL). Strain BbR2 was the fastest growing strain on almost all nutrient sources studied and possessed commendable growth rate and sporulation potential. Wheat bran (WB) and rice bran (RB) in the proportion of 3:1 supported maximum conidiospores yields (1.90x107 conidia/mL) for strain BbR2 in solid state fermentation conditions.

Isolation and evaluation of potent Pseudomonas species for bioremediation of phorate in amended soil.

Use of phorate as a broad spectrum pesticide in agricultural crops is finding disfavor due to persistence of both the principal compound as well as its toxic residues in soil. Three phorate utilizing bacterial species (Pseudomonas sp. strain Imbl 4.3, Pseudomonas sp. strain Imbl 5.1, Pseudomonas sp. strain Imbl 5.2) were isolated from field soils. Comparative phorate degradation analysis of these species in liquid cultures identified Pseudomonas sp. strain Imbl 5.1 to cause complete metabolization of phorate during seven days as compared to the other two species in 13 days. In soils amended with phorate at different levels (100, 200, 300 mg kg(-1) soil), Pseudomonas sp. strain Imbl 5.1 resulted in active metabolization of phorate by between 94.66% and 95.62% establishing the same to be a potent bacterium for significantly relieving soil from phorate residues. Metabolization of phorate to these phorate residues did not follow the first order kinetics. This study proves that Pseudomonas sp. strain Imbl 5.1 has huge potential for active bioremediation of phorate both in liquid cultures and agricultural soils.

Brevibacterium frigoritolerans as a Novel Organism for the Bioremediation of Phorate.

Phorate, an organophosphorus insecticide, has been found effective for the control of various insect pests. However, it is an extremely hazardous insecticide and causes a potential threat to ecosystem. Bioremediation is a promising approach to degrade the pesticide from the soil. The screening of soil from sugarcane fields resulted in identification of Brevibacterium frigoritolerans, a microorganism with potential for phorate bioremediation was determined. B. frigoritolerans strain Imbl 2.1 resulted in the active metabolization of phorate by between 89.81% and 92.32% from soils amended with phorate at different levels (100, 200, 300 mg kg(-1) soil). But in case of control soil, 33.76%-40.92% degradation were observed. Among metabolites, sulfone was found as the main metabolite followed by sulfoxide. Total phorate residues were not found to follow the first order kinetics. This demonstrated that B. frigoritolerans has potential for bioremediation of phorate both in liquid cultures and agricultural soils.

Thiamethoxam degradation by Pseudomonas and Bacillus strains isolated from agricultural soils.

Twelve bacterial species were evaluated to know the degradation pattern of thiamethoxam in liquid medium. All the bacterial species could actively degrade phorate in a mineral salt medium containing phorate (50 µg ml(-1)) as sole carbon source. As these species have ability to degrade, we used these for the degradation of thiamethoxam--a neonicoitinoids. Screening of 12 active phorate-metabolizing bacterial species resulted in selection of Bacillus aeromonas strain IMBL 4.1 and Pseudomonas putida strain IMBL 5.2 causing 45.28 and 38.23 % thiamethoxam (50 µg ml(-1)) reduction, respectively, in 15 days as potential thiamethoxam degrading species. These two bacterial species grew optimally at 37 °C under shake culture conditions in MSMT medium raised with initial pH of 6.0-6.5 and use of these optimum cultural conditions resulted in improved thiamethoxam degradation by these bacterial species. These species caused maximum thiamethoxam degradation only in the presence of thiamethoxam as sole source of carbon and energy and the same was reduced in the presence of easily metabolize able carbon (C0 and C1) and nitrogen ((N0, N1 and N2) sources. This could be attributed to involvement of repressible metabolic pathways, reactions of which are inhibited by the presence of easily available nutrients for growth. Besides above, qualitative analysis of thiamethoxam residues by gas liquid chromatography revealed complete metabolization of thiamethoxam without detectable accumulation of any known thiamethoxam metabolites.

Prospective Case-Control Study to Evaluate the Role of Glutathione S Transferases (GSTT1 and GSTM1) Gene Deletion in Breast Carcinoma and Its Prognostic Significance.

Breast cancer is the most common cause of cancer death in women with the incidence rising in young women. GST gene polymorphisms are significant because of their role in the detoxification of both environmental carcinogens and also cytotoxic drugs used in therapy for breast cancer. The present study has been designed to identify the role of polymorphisms in GSTT1 and GSTM1 genes in the risk of development of breast cancer, in the prognostication of breast cancer, and in the prediction of response towards chemotherapy. Ninety-nine patients with breast cancer and 100 healthy controls with no history of cancer were taken from blood donors after informed consent. Epidemiological and clinical data was collected from participants and 5 ml of peripheral venous blood was collected for genotype analysis. Null genotype of GSTT1 was detected in 51.04 % of the controls in comparison to 20.2 % of patients with carcinoma breast, which was found to be statistically significant (OR 4.18; 95 % CI 2.01-8.75; P = 0.0001). GSTM1 gene deletion was also significantly more common among controls (60 %) than in patients with breast cancer (33 %) (OR 4.57; 95 % CI 2.20-9.51; P = 0.0001). Tumors more than 5 cm in size had greater tendency for GSTM1 gene expression (P value = 0.019), but other clinicopathological parameters did not show any correlation. GSTT1 and GSTM1 genes status did not show any association with response to chemotherapy. The results indicated the null genotype of both GSTT1 and GSTM1 to be protective for the development of carcinoma breast. None of the known etiological factors have any correlation with GSTT1 and GSTM1 gene deletion. Patients with small tumor size expressed GSTM1 gene deletion. Other tumor characteristics and clinicopathological parameters did not have any correlation with gene deletion.