41 results on '"Mittal, Balraj"'
Search Results
2. A multigenic approach to evaluate genetic variants of PLCE1, LXRs, MMPs, TIMP, and CYP genes in gallbladder cancer predisposition
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Sharma, Kiran Lata, Rai, Rajani, Srivastava, Anshika, Sharma, Aarti, Misra, Sanjeev, Kumar, Ashok, and Mittal, Balraj
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- 2014
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3. Association of genetic variants of xenobiotic and estrogen metabolism pathway (CYP1A1 and CYP1B1) with gallbladder cancer susceptibility
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Sharma, Kiran Lata, Agarwal, Akash, Misra, Sanjeev, Kumar, Ashok, Kumar, Vijay, and Mittal, Balraj
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- 2014
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4. PLCE1 rs2274223 A>G polymorphism and cancer risk: a meta-analysis
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Umar, Meenakshi, Upadhyay, Rohit, and Mittal, Balraj
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- 2013
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5. K121Q ENPP1/PC-1 gene polymorphism is associated with insulin resistance in a north Indian population
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PRAKASH, JAI, MITTAL, BALRAJ, AWASTHI, SHALLY, AGARWAL, C. G., and SRIVASTAVA, NEENA
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- 2013
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6. Role of genetic variants of deleted in colorectal carcinoma (DCC) polymorphisms and esophageal and gastric cancers risk in Kashmir Valley and meta-analysis
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Malik, Manzoor Ahmad, Gupta, Annapurna, Zargar, Showkat Ali, and Mittal, Balraj
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- 2013
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7. Survivin promoter −31G/C (rs9904341) polymorphism and cancer susceptibility: a meta-analysis
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Srivastava, Kshitij, Srivastava, Anvesha, and Mittal, Balraj
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- 2012
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8. Pharmacogenetic Aspects of Coumarinic Oral Anticoagulant Therapies
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Rathore, Saurabh Singh, Agarwal, Surendra Kumar, Pande, Shantanu, Singh, Sushil Kumar, Mittal, Tulika, and Mittal, Balraj
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- 2011
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9. Influence of Bcl-1 Gene Polymorphism of Glucocorticoid Receptor Gene (NR3C1, rs41423247) on Blood Pressure, Glucose in Northern Indians
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Srivastava, Neena, Prakash, Jai, Lakhan, Ram, Agarwal, C. G., Pant, D. C., and Mittal, Balraj
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- 2011
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10. DNMT3B −579 G>T Promoter Polymorphism and Risk of Gallbladder Carcinoma in North Indian Population
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Srivastava, Kshitij, Srivastava, Anvesha, and Mittal, Balraj
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- 2010
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11. A common polymorphism in the promoter of UCP2 is associated with obesity and hyperinsulenemia in northern Indians
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Srivastava, Neena, Prakash, Jai, Lakhan, Ram, Agarwal, C. G., Pant, D. C., and Mittal, Balraj
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- 2010
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12. Functional polymorphisms of the cyclooxygenase (PTGS2) gene and risk for gallbladder cancer in a North Indian population
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Srivastava, Kshitij, Srivastava, Anvesha, Pandey, Sachchida Nand, Kumar, Ashok, and Mittal, Balraj
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- 2009
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13. Role of cyclooxygenase-2 functional gene polymorphisms in Helicobacter pylori induced gastritis and gastric atrophy
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Achyut, B. R., Ghoshal, Uday C., Moorchung, Nikhil, and Mittal, Balraj
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- 2009
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14. Interleukin-10 (−819 C/T) and Tumor Necrosis Factor-α (−308 G/A) Gene Variants Influence Gastritis and Lymphoid Follicle Development
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Achyut, B. R., Tripathi, Priya, Ghoshal, Uday Chand, Moorchung, Nikhil, and Mittal, Balraj
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- 2008
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15. Is IL-10 −819C/T Gene Polymorphism Modulating the Risk of Gallbladder Disease in North Indian Population?
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Vishnoi, Monika, Choudhuri, Gourdas, and Mittal, Balraj
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- 2007
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16. Association of the −243A>G, +61450C>A Polymorphisms of the Glutamate Decarboxylase 2 (GAD2) Gene with Obesity and Insu¬lin Level in North Indian Population
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PRAKASH, Jai, MITTAL, Balraj, AWASTHI, Shally, and SRIVASTAVA, Neena
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GAD-2 ,Food intake ,lcsh:Public aspects of medicine ,Insulin ,Original Article ,lcsh:RA1-1270 ,Obesity ,Polymorphism - Abstract
Background: Obesity associated with type 2 diabetes, and hypertension increased mortality and morbidity. Glutamate decarboxylase 2 (GAD2) gene is associated with obesity and it regulate food intake and insulin level. We investigated the association of GAD-2gene −243A>G (rs2236418) and +61450C>A (rs992990) polymorphisms with obesity and related phenotypes.Methods: Insulin, glucose and lipid levels were estimated using standard protocols. All subjects were genotyped (PCR-RFLP) method.Results: The −243A>G polymorphism of the GAD-2 gene was significantly associated with higher risk of obesity (PConclusion: GAD-2 gene polymorphisms influence obesity and related phenotype in complex manner, probably by regulating the food intake, insulin and body weight. Keywords: Obesity, Insulin, GAD-2, Food intake, Polymorphism
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- 2016
17. The Association of a Rare Variant of -93, -53 Promoter Gene Polymorphisms of Lipoprotein Lipase Gene with Obesity and Insulin Resistance.
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Prakash, Jai, Mittal, Balraj, Srivastava, Apurva, Awasthi, Shally, and Srivastava, Neena
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STATISTICAL correlation , *DIABETES , *GENETIC polymorphisms , *INSULIN resistance , *LIPOPROTEINS , *OBESITY - Abstract
Objectives: Obesity increases the risk of numerous chronic diseases. Obesity is classified clinically using body mass index (BMI), waist-to-hip ratio, and body fat percentage. The lipoprotein lipase (LPL) gene has been linked to lipoprotein metabolism and obesity. We performed a case-control study to determine the association between LPL gene polymorphisms and obesity-associated phenotypes such as insulin resistance (IR). Methods: We examined the different LPL gene variants for association in 642 individuals segregated by BMI and IR. Genotyping of the LPL gene -93 and -53 promoter gene polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism. Results: A substantial association was observed for -93 gene polymorphism of the LPL gene with obesity, while -53 promoter gene polymorphism showed association with IR. Conclusions: We found a significant association between -93 and -53 promoter gene polymorphisms of the LPL gene with obesity and associated phenotypes in the studied population. [ABSTRACT FROM AUTHOR]
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- 2018
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18. Effect of Genetic Variant (rs11887534) in ABCG8 Gene in Coronary Artery Disease and Response to Atorvastatin Therapy
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Srivastava, Anshika, Garg, Naveen, Srivastava, Anvesha, Srivastava, Kshitij, and Mittal, Balraj
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Male ,Genotype ,Coronary Artery Disease ,ABCG8 ,Polymerase Chain Reaction ,polymorphism ,PCR-RFLP ,Risk Factors ,Atorvastatin ,Humans ,Genetic Predisposition to Disease ,Pyrroles ,cardiovascular diseases ,lcsh:R5-920 ,Polymorphism, Genetic ,Anticholesteremic Agents ,ATP Binding Cassette Transporter, Subfamily G, Member 8 ,Middle Aged ,Lipids ,Treatment Outcome ,Heptanoic Acids ,Case-Control Studies ,Atorvastatin therapy ,ATP-Binding Cassette Transporters ,Female ,lipids (amino acids, peptides, and proteins) ,Other ,lcsh:Medicine (General) - Abstract
Background: ATP-binding cassette transporter ABCG8 plays an important role in excretion of cholesterol from liver. Common genetic polymorphisms in ABCG8 gene may genetically predispose an individual to coronary artery disease (CAD) along with response to atorvastatin therapy. Thus, we aimed to examine the role of ABCG8 D19H polymorphism (rs11887534) in susceptibility to CAD and its influence on atorvastatin response. Methodology: The study included 213 CAD patients and 220 controls. Genotyping of ABCG8 D19H polymorphism was done by PCR-RFLP. Results: Our results showed that ABCG8 ‘H’ allele was conferring significant risk for CAD in a dominant model (OR = 2.54; p = 0.014). This increased risk for CAD was more pronounced in males (OR = 2.69; p = 0.030). No correlation of ABCG8 genotypes with the risk factors (diabetes, hypertension and smoking) of CAD was observed. On atorvastatin treatment there was a significant decrease in the LDL-C levels (p = 0.021). However, stepwise multiple regression analysis showed that this decease was not associated with ABCG8 genetic variant (p = 0.845). Observed determinants of variation in interindividual response to atorvastatin therapy were pre-treatment LDL-C (p = 0.024) and TC (p = 0.017). Conclusion: Although the genetic variant 19H of ABCG8 confers risk for CAD in North Indian population, it is not associated with interindividual response to atorvastatin therapy.
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- 2010
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19. Impact of DCC (rs714) and PSCA (rs2294008 and rs2976392) Gene Polymorphism inModulating Cancer Risk in Asian Population.
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Chandra, Vishal, Jong Joo Kim, Gupta, Usha, Mittal, Balraj, and Rai, Rajani
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GENETIC polymorphisms ,CANCER risk factors ,CANCER genetics ,COLON cancer ,BIOMARKERS ,DISEASE susceptibility - Abstract
Multiple studies have investigated the association of gene variant of Deleted in colorectal carcinoma (DCC) and Prostate Stem cell antigen (PSCA) with various cancer susceptibility; however, the results are discrepant. Since SNPs are emerging as promising biomarker of cancer susceptibility, here, we aimed to execute a meta-analysis of DCC (rs714 A > G) and PSCA (rs2294008 C > T, rs2976392 G > A) polymorphism to demonstrate the more accurate strength of these associations. We followed a rigorous inclusion/exclusion criteria and calculated the pooled odds ratios (ORs) and 95% confidence intervals (CIs). Overall, the pooled analysis showed that the DCC rs714 conferred increased risk of cancer only in Asians (AA vs. GG: OR = 1.86, p ≤ 0.0001; AG vs. GG: OR = 1.43, p = 0.005; GA + AA vs. GG: OR = 1.66, p ≤ 0.0001; AA vs. GG + GA; OR = 1.52, p ≤ 0.004, A vs. G allele: OR = 1.41, p ≤ 0.0001). PSCA rs2294008 was associated with increased overall cancer risk (TT vs. CC: OR = 1.28, p = 0.002; CT vs. CC: OR = 1.21, p ≤ 0.0001; CT + TT vs. CC: OR = 1.24, P ≤ 0.0001; TT vs. CC + CT; OR = 1.17, p ≤ 0.005, T vs. C allele: OR = 1.16, p ≤ 0.0001); however, in stratified analysis this association was limited only to gastric and bladder cancer and the strength was more prominent in Asians. In contrast, the PSCA rs2976392 SNP did not modulate the cancer risk. Therefore, we concluded that rs714 and rs2294008 polymorphism may represent a potential genetic biomarker for cancer risk in Asians and gastric as well as bladder cancer, respectively. However, since our study is limited to Asians and cancer types, further larger studies involving other cancers and/or population, gene-environment interactions and the mechanism of DCC and PSCA gene deregulation are desired to define the role of genotype with overall cancer risk. [ABSTRACT FROM AUTHOR]
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- 2016
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20. A Multiple Interaction Analysis Reveals ADRB3 as a Potential Candidate for Gallbladder Cancer Predisposition via a Complex Interaction with Other Candidate Gene Variations.
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Rai, Rajani, Jong Joo Kim, Misra, Sanjeev, Kumar, Ashok, and Mittal, Balraj
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GALLBLADDER cancer ,GENETIC polymorphisms ,CARCINOGENESIS ,CANCER education ,INCURABLE diseases - Abstract
Gallbladder cancer is the most common and a highly aggressive biliary tract malignancy with a dismal outcome. The pathogenesis of the disease is multifactorial, comprising the combined effect of multiple genetic variations of mild consequence along with numerous dietary and environmental risk factors. Previously, we demonstrated the association of several candidate gene variations with GBC risk. In this study, we aimed to identify the combination of gene variants and their possible interactions contributing towards genetic susceptibility of GBC. Here, we performed Multifactor-Dimensionality Reduction (MDR) and Classification and Regression Tree Analysis (CRT) to investigate the gene-gene interactions and the combined effect of 14 SNPs in nine genes (DR4 (rs20576, rs6557634); FAS (rs2234767); FASL (rs763110); DCC (rs2229080, rs4078288, rs7504990, rs714); PSCA (rs2294008, rs2978974); ADRA2A (rs1801253); ADRB1 (rs1800544); ADRB3 (rs4994); CYP17 (rs2486758)) involved in various signaling pathways. Genotyping was accomplished by PCR-RFLP or Taqman allelic discrimination assays. SPSS software version 16.0 and MDR software version 2.0 were used for all the statistical analysis. Single locus investigation demonstrated significant association of DR4 (rs20576, rs6557634), DCC (rs714, rs2229080, rs4078288) and ADRB3 (rs4994) polymorphisms with GBC risk. MDR analysis revealed ADRB3 (rs4994) to be crucial candidate in GBC susceptibility that may act either alone (p < 0.0001, CVC = 10/10) or in combination with DCC (rs714 and rs2229080, p < 0.0001, CVC = 9/10). Our CRT results are in agreement with the above findings. Further, in-silico results of studied SNPs advocated their role in splicing, transcriptional and/or protein coding regulation. Overall, our result suggested complex interactions amongst the studied SNPs and ADRB3 rs4994 as candidate influencing GBC susceptibility. [ABSTRACT FROM AUTHOR]
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- 2015
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21. Achalasia Is Associated With eNOS4a4a, iNOS22GA, and nNOS29TT Genotypes: A Case-control Study.
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Singh, Rajan, Ghoshal, Uday C., Misra, Asha, and Mittal, Balraj
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ESOPHAGEAL achalasia ,ESOPHAGUS diseases ,ESOPHAGEAL atresia ,POLYMERASE chain reaction ,RESTRICTION fragment length polymorphisms ,THERAPEUTICS - Abstract
Background/Aims: Achalasia is known to result from degeneration of inhibitory neurons, which are mostly nitrinergic. Characteristic features of achalasia include incomplete lower esophageal sphincter (LES) relaxation and esophageal aperistalsis. Nitric oxide (NO), produced by NO synthase (NOS), plays an important role in peristalsis and LES relaxation. Therefore, we evaluated genetic polymorphisms of NOS gene isoforms (endothelial NOS [eNOS], inducible NOS [iNOS], and neuronal NOS [nNOS]) in patients with achalasia and healthy subjects (HS). Methods: Consecutive patients with achalasia (diagnosed using esophageal manometry) and HS were genotyped for 27-base pair (bp) eNOS variable number of tandem repeats (VNTR), iNOS22G/A (rs1060826), nNOS C/T (rs2682826) polymorphisms by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP), respectively. Results: Among 183 patients (118 [64.5%] male, age 39.5 ± 13.0 years) with achalasia and 366 HS (254 [69.4%] male, age 40.8 ± 11.0 years), eNOS4a4a genotype of 27-bp VNTR was more common among achalasia than HS (20 [10.9%] vs 13 [3.6%]; P < 0.001; OR, 3.72; 95% CI, 1.8-7.7). Patients with achalasia had iNOS22GA genotypes more often than HS (95 [51.9%] vs 93 [25.4%]; P < 0.001; OR, 3.0; 95% CI, 2.1-4.4). Frequency of genotypes GA + AA was higher in patients than HS (97 [53%] vs 107 [29.2%]; P < 0.001; OR, 2.7; 95% CI, 1.8-3.9). Also, nNOS29TT variant genotype in rs2682826 was more com - mon among patients compared to HS (14 [7.7%] vs 6 [1.6%]; P < 0.001; OR, 5.91; 95% CI, 2.2-15.8). Conclusions: Achalasia is associated with eNOS4a4a, iNOS22GA, and nNOS29TT genotypes. This may suggest that polymorphisms of eNOS, iNOS, and nNOS genes are risk factors for achalasia. [ABSTRACT FROM AUTHOR]
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- 2015
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22. Association of Adiponectin Gene Polymorphism with Adiponectin Levels And Risk for Insulin Resistance Syndrome.
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Prakash, Jai, Mittal, Balraj, Awasthi, Shally, and Srivastava, Neena
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ADIPONECTIN , *GENETIC polymorphisms , *POLYMERASE chain reaction , *INSULIN resistance , *HAPLOTYPES - Abstract
Background: Adiponectin is an abundant adipose tissue-derived protein with anti-atherogenic, anti-inflammatory and antidiabetic properties. Plasma adiponectin levels are decreased in obesity, type 2 diabetes, and coronary artery disease and low adiponectin levels also predict insulin resistance (IR). Methods: Case-control study in which 642 male and female subjects were participated from the North Indian population. Lipid, insulin, leptin and adiponectin level were estimated using standard protocols by commercially available test kits. Single nucleotide polymorphisms +45T>G and +276G>T of the AMP1 (adiponectin) gene was genotyped by polymerase chain reaction restriction fragment length polymorphism method. Results: Levels of adiponectin, insulin, homeostasis model assessment-IR index (HOMA-IR index), systolic blood pressure and fat mass showed significant differences between male and female subjects. Serum adiponectin level showed highly significant association with both the +45 and the +276 genotypes. The common haplotype triglyceride (TG) showed a significantly lower adiponectin value than other haplotypes (P = 0.0001). A clear trend of decreasing adiponectin levels per copy of the common haplotype was observed. Nonobese insulin sensitive subjects showed a higher adiponectin value (P = 0.0006) than nonobese insulin resistant subjects. The values of blood pressure, adiponectin, insulin, HOMA-IR, total-cholesterol, and low-density lipoprotein-cholesterol significantly associated with TG haplotype. Conclusions: We observed the very strong association of the adiponectin 45-276 genotypes and haplotypes with adiponectin levels in healthy north Indian population and TG haplotypes also associated with metabolic parameters of the IR syndrome. [ABSTRACT FROM AUTHOR]
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- 2015
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23. PLCE1 rs2274223 A>G polymorphism and cancer risk: a meta-analysis.
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Umar, Meenakshi, Upadhyay, Rohit, and Mittal, Balraj
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Phospholipase C epsilon 1 gene ( PLCE1) encodes a phospholipase enzyme which regulates various physiological processes (cell growth, differentiation, and apoptosis) and is supposed to play a critical role in carcinogenesis. Recently, a single nucleotide polymorphism (rs2274223 A>G) in PLCE1 was reported as a novel susceptibility locus for esophageal and gastric cancers by genome-wide association studies performed in Chinese population. However, individual association studies replicating this finding showed inconclusive results. Therefore, we performed a meta-analysis of eligible studies to derive precise estimation of the association of PLCE1 rs2274223 A>G polymorphism with cancer risk. We performed pooled analysis of 12 case–control studies including 7,622 cases and 9,555 controls. Odds ratios and 95 % confidence interval were calculated to assess strength of association in overall studies and in subgroup analysis stratified by ethnicity, cancer types, and source of controls. All statistical analyses were performed by MIX 2.0 software. We found that PLCE1 rs2274223 A>G polymorphism was significantly associated with increased risk of cancer in log additive/dominant model and at allele level (GG vs. AA: OR = 1.24, 95 % CI = 1.01–1.53, P = 0.039; AG vs. AA: OR = 1.24, 95 % CI = 1.16–1.32, P < 0.001; AG + GG vs. AA: OR = 1.22, 95 % CI = 1.12–1.34, P < 0.001; and G vs. A allele: OR = 1.15, 95 % CI = 1.05–1.25, P = 0.002). Further, stratified analysis showed elevated risk of only gastric and esophageal tumors. Sub-group analysis based on ethnicity suggests PLCE1 polymorphism conferred significant risk among Asian (Chinese) but not in Caucasian. In conclusion, PLCE1 rs2274223 polymorphism may be used as potential biomarker for cancer susceptibility particularly for esophageal/gastric cancer and for the Chinese population. [ABSTRACT FROM AUTHOR]
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- 2013
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24. Association of FTO rs17817449 SNP with obesity and associated physiological parameters in a north Indian population.
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Prakash, Jai, Srivastava, Neena, Awasthi, Shally, Agarwal, C. G., Natu, S. M., Rajpal, Naresh, and Mittal, Balraj
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OBESITY risk factors ,TYPE 2 diabetes ,HYPERTENSION ,ATHEROSCLEROSIS ,BODY mass index ,EUROPEANS ,GENOTYPE-environment interaction ,GENETIC polymorphisms ,DISEASES - Abstract
Background: Obesity is a very common disorder directly linked with various diseases such as type-2 diabetes, hypertension and atherosclerosis. Variants in the FTO gene have been associated with Body Mass Index in Western European and North American populations. Aim: This study analysed the association between the FTO gene variant rs17817449 (G>T) and obesity and obesity-related phenotypes in a north Indian population. Subjects and methods: A total of 642 subjects, 309 obese and 333 non-obese individuals, were included in this case-control study. Genotyping of FTO gene (rs17817449) polymorphism for all subjects was performed by the PCR-RFLP method. Results: Significant associations were found for FTO rs17817449 SNP with obesity and obesity-related phenotypes. The strongest associations were observed between the rs17817449 and fasting blood glucose, insulin, homeostasis model of assessment-insulin resistance (HOMA-IR) and fat mass under a recessive model. Conclusions: This study replicated the genetic association of SNP of FTO (rs17817449) with obesity in a north Indian population and, to the authors' knowledge; this is the first such association study in a north Indian population. This study also established that SNP in intron 1 of FTO (rs17817449) are strongly associated with several measures of adiposity and are also associated with plasma insulin, insulin resistance, percentage body fat and fat mass. [ABSTRACT FROM AUTHOR]
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- 2011
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25. Role of ABCG8 D19H (rs11887534) variant in gallstone susceptibility in northern India A Srivastava et al. ABCG8 D19H polymorphism and gallstone disease.
- Author
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Srivastava, Anshika, Srivastava, Anvesha, Srivastava, Kshitij, Choudhuri, Gourdas, and Mittal, Balraj
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GALLSTONES ,GENETIC polymorphisms ,BILE ,CHOLESTEROL ,CHOLECYSTECTOMY - Abstract
The excretion of cholesterol from the liver is regulated by the ATP-binding cassette transporter ABCG8. A common genetic polymorphism D19H of ABCG8 might be related to the genetic predisposition of gallstone disease, which is causatively related to supersaturation of cholesterol in bile. We aimed to examine the role of the ABCG8 D19H (rs11887534) polymorphism in susceptibility to gallstone disease in the northern Indian population. The study included 220 confirmed gallstone patients and 230 controls. Genotyping for the ABCG8 D19H polymorphism was carried out using the PCR-RFLP method. We observed that the ABCG8 DH genotype frequency was significantly higher in gallstone patients ( P = 0.038; odds ratio [OR] = 2.20; 95% confidence interval [CI] = 1.1-4.6). At allele level also, the ABCG8 variant allele conferred an increased risk for gallstone susceptibility ( P = 0.043; OR = 2.12; 95% CI = 1.2-4.3). The risk as a result of ABCG8 D19H variation was more pronounced in female gallstone patients at genotype ( P = 0.026; OR = 3.01, 95% CI = 1.1-7.9) as well as allele level ( P = 0.030; OR = 2.85; 95% CI = 1.1-7.3). However, the molecular modeling results of the rs11887534 polymorphism showed that the overall configuration of both wild-type and polymorphic ABCG8 protein were similar, with negligible deviation at the site of polymorphism. Carriers of the DH genotype and H allele of the ABCG8 D19H polymorphism harbor a higher risk for gallstone susceptibility in the northern Indian population. [ABSTRACT FROM AUTHOR]
- Published
- 2010
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26. Common genetic variants in pre-microRNAs and risk of gallbladder cancer in North Indian population.
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Srivastava, Kshitij, Srivastava, Anvesha, and Mittal, Balraj
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GENETIC research ,GALLBLADDER diseases ,GENETIC polymorphisms - Abstract
MicroRNAs (miRNAs) are small, non-coding RNA molecules that function as negative regulators of gene expression. Common genetic variants (single nucleotide polymorphisms, SNPs) in miRNA genes may alter their expression or maturation resulting in varied functional consequences. Present case–control study evaluated the potential association of three SNPs (rs2910164, rs11614913 and rs3746444) in pre-miRNAs with gallbladder cancer (GBC) risk in 230 GBC cases and 230 controls in a North Indian population. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated for the association of individual SNPs and their interactions with GBC. A non-significant increased risk was observed between carriers of variant genotypes of rs2910164, rs11614913 and rs3746444 (ORs=1.3, 1.3 and 1.1, respectively). This increased risk was more profound in GBC patients with gallstones (ORs=1.4, 1.6 and 1.1, respectively). To further evaluate the cumulative effects of the variant allele, we did a combined unfavorable genotype analysis, which showed a borderline statistical significance. In comparison with the low-risk group (0–2 variant alleles), the high-risk group (>2 variant alleles) had a 1.7-fold (95% CI=1.0–2.8) increased risk for GBC (P
trend =0.056). These findings suggest, for the first time, that common miRNA variants may not contribute to GBC susceptibility in North Indian population. [ABSTRACT FROM AUTHOR]- Published
- 2010
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27. Significant association between toll-like receptor gene polymorphisms and gallbladder cancer.
- Author
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Srivastava, Kshitij, Srivastava, Anvesha, Kumar, Ashok, and Mittal, Balraj
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GENETIC polymorphisms ,CELL receptors ,CANCER susceptibility ,GALLBLADDER cancer ,COLON cancer ,RESTRICTION fragment length polymorphisms - Abstract
Background: Toll-like receptors (TLRs) are evolutionarily conserved cell surface receptors of innate immune system. Various polymorphisms in TLR genes have been identified and associated with susceptibility toward various malignancies such as prostate cancer, gastric cancer and colorectal cancer. The present study was undertaken to examine the potential association of two polymorphisms in TLR2 and TLR4 genes with gallbladder cancer (GBC) susceptibility. Methods: Genotypes and allelic frequencies of TLR2 and TLR4 gene polymorphisms were determined for 233 GBC patients and 257 cancer-free controls randomly selected from the population, using polymerase chain reaction–restriction fragment length polymorphism. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated in a multivariate logistic regression analysis for the association of TLR polymorphisms with GBC. Results: ‘del’ allele carriers of TLR2 (Δ22) polymorphism were associated with a 1.54-fold increased risk for GBC (95% CI=1.02–2.24; P
trend =0.091). The TLR4 Ex4+936C >T polymorphism (g.14143C>T; rs4986791) was also found to be significantly associated with the overall higher risk of GBC under a dominant mode of inheritance (OR=1.96; 95% CI=1.11–2.26; Ptrend =0.021). The false-positive report probability (FPRP) approach advocated that these results were noteworthy ( FPRP<0.5). Subgroup analysis showed that TLR4 Ex4+936C>T polymorphism was associated with an increased risk of GBC in females and GBC cases with gallstones (OR=2.85 and 2.22 respectively). Conclusion: In summary, low-penetrance variants in TLR genes may alter the susceptibility towards gallbladder cancer. [ABSTRACT FROM AUTHOR]- Published
- 2010
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28. Polymorphisms in ERCC2, MSH2, and OG DNA Repair Genes and Gallbladder Cancer Risk in a Population of Northern India.
- Author
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Srivastava, Kshitij, Srivastava, Anvesha, and Mittal, Balraj
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GENETIC polymorphism research ,GALLBLADDER cancer ,CANCER genetics ,CANCER risk factors ,DNA repair - Abstract
The article discusses a study which examined the association between polymorphisms in ERCC2, MSH2 and OGG1 DNA repair genes and gallbladder cancer. The study included 230 patients with gallbladder cancer and 230 controls. Study authors found that ERCC2, MSH2 and OGG1 genotypes are associated with increased risk of GB carcinogenesis. They concluded that the genetic variants in the DNA repair pathways seemed to be involved in GB carcinogenesis etiology.
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- 2010
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29. Single nucleotide polymorphism in the ABCG8 transporter gene is associated with gallbladder cancer susceptibility.
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Srivastava, Anvesha, Tulsyan, Sonam, Pandey, Sachchida Nand, Choudhuri, Gourdas, and Mittal, Balraj
- Subjects
POLYMERASE chain reaction ,NUCLEOTIDE analysis ,GENETIC polymorphisms ,GALLBLADDER cancer ,HOMEOSTASIS ,PHYSIOLOGICAL control systems - Abstract
Background: Gallbladder cancer (GBC) usually arises against the background of gallstone disease, which may be causatively related to supersaturation of cholesterol in bile. An imbalance in cholesterol homeostasis because of oversecretion of cholesterol in the gallbladder promotes gallstone formation. The excretion of cholesterol from the liver is regulated by adenosine triphosphate-binding cassette transporter ABCG8. A common genetic polymorphism D19H of ABCG8 associated with gallstone disease may be causatively related to the genetic predisposition of GBC. Aim: We aimed to examine the role of ABCG8 D19H (rs11887534) polymorphism in susceptibility to GBC. Methodology: This study included 171 confirmed GBC patients and 221 controls. Genotyping for the ABCG8 D19H polymorphism was performed by the polymerase chain reaction-restriction fragment length polymorphism method. Results: We observed that in our population the ABCG8 DH genotype frequency was significantly higher in GBC patients [ P=0.011; odds ratio (OR)=1.79; 95% confidence interval (CI)=1.1–2.8]. Also, at the allele level, ABCG8H conferred an increased risk for GBC ( P=0.023; OR=1.60; 95% CI=1.0–2.4). The risk was more pronounced in GBC patients with gallstones ( P=0.027; OR=1.85; 95% CI=1.0–3.1), and in patients with an early onset of the disease ( P=0.013; OR=2.55, 95% CI=1.2–5.3). However, there was no modulation of GBC risk because of the ABCG8 polymorphism in a gender-specific manner. Conclusion: The results suggest that the DH genotype and the H allele of the ABCG8 D19H polymorphism are associated with GBC susceptibility. The GBC patients with gallstone disease harbouring the ABCG8 variant allele are at a higher risk, while the effect of this polymorphism on GBC patients without gallstones appears to be small. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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30. Cholecystokinin receptor A gene polymorphism in gallstone disease and gallbladder cancer.
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Srivastava, Anvesha, Pandey, Sachchida Nand, Dixit, Manjusha, Choudhuri, Gourdas, and Mittal, Balraj
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GALLSTONES ,BILE duct diseases ,GALLBLADDER diseases ,CHOLECYSTOKININ ,GASTROINTESTINAL hormones ,NEUROPEPTIDES ,GENETIC polymorphisms - Abstract
Background and Aim: Gallbladder carcinoma (GBC) usually arises in the background of gallstone disease which may be causatively related to decreased gallbladder contractility. Cholecystokinin receptor A ( CCK-AR) mediates signals resulting in gallbladder contraction. Deteriorating gallbladder contraction promotes gallstone formation. A common genetic polymorphism of CCK-AR may be causatively associated with the risk of gallstone and GBC. This study aimed to understand the association of CCK-AR Pst I polymorphism in gallstone disease with gallbladder cancer. Method: This study included 165 gallstone patients, 139 GBC patients, and 190 healthy subjects. Genotyping was done using the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method. Results: The frequency of the A1A1 genotype of CCK-AR was significantly higher in gallstone patients than healthy individuals ( P = 0.008 odds ratio [OR] = 2.25, and 95% confidence interval [CI]:1.2–4.1). However, there was a significant difference in the frequency of A1A1 genotype when gallstone patients were compared to GBC patients ( P = 0.041, OR = 0.49, and 95% CI: 0.3–0.9). On stratification of GBC patients according to presence or absence of gallstones, GBC patients without stones were compared to controls and GBC patients with stones were compared to stone patients; however, no significant differences in frequencies were observed. Conclusion: The results suggest that the A1A1 genotype of CCK-AR is an independent genetic risk factor for gallstone disease and does not modulate the susceptibility of gallbladder cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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31. MMP-7 (−181A>G) promoter polymorphisms and risk for cervical cancer
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Singh, HariOm, Jain, Meenu, and Mittal, Balraj
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CERVICAL cancer , *METALLOPROTEINASES , *NEOVASCULARIZATION , *GENETIC polymorphisms - Abstract
Abstract: Objectives: Matrix metalloproteinase (MMP-7) is a secreted matrilysin, which contributes to tumor progression through breakdown of basement membranes and angiogenesis. Therefore, we aimed to investigate the association of MMP-7 −181A>G gene polymorphism with risk of cervical cancer. Methods: In the present case control study, we enrolled a total of 150 cervical cancer patients confirmed by histopathology and 162 unrelated healthy individuals. Polymorphism for MMP-7 gene (−181A>G) was genotyped by polymerase chain reaction and restriction enzyme length polymorphism. Results: Frequency of MMP-7 −181GG genotype and − 181G allele differed significantly between patients with cervical cancer (29.3%) and healthy individuals (19.4%) (P =0.041; OR GG =1.94 and P =0.048; OR G =1.94). Individuals with MMP-7 −181GG genotype were at higher risk of stage II of cervical cancer with borderline significance (P =0.05, OR=2.78; 95%CI: 0.89–8.69). However, interaction of MMP-7 −181AG and GG genotypes with tobacco usage did not modulate the cervical cancer risk significantly (OR 2.21, 95%CI=0.59–8.1 and OR 3.17, 95%CI=0.64–15.7). Conclusion: Individuals with MMP-7 −181GG genotype were at significantly higher risk of cervical cancer. [Copyright &y& Elsevier]
- Published
- 2008
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32. CYP4F2 1347 G>A & GGCX 12970 C>G polymorphisms: frequency in north Indians & their effect on dosing of acenocoumarol oral anticoagulant.
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Rathore, Saurabh Singh, Agarwal, Surendra Kumar, Pande, Shantanu, Singh, Sushil Kumar, Mittal, Tulika, and Mittal, Balraj
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GENETIC polymorphism research , *CARBOXYLASES , *ANTICOAGULANTS , *PHARMACOGENOMICS , *BIOCHEMICAL genetics - Abstract
Background & objectives: CYP4F2 and γ-glutamyl carboxylase (GGCX) have small but significant roles in the maintenance dose of coumarinic oral anticoagulants (COAs). CYP4F2 1347 G>A and GGCX 12970 C>G polymorphisms have been used in the pharmacogenetic dosing algorithms of warfarin for Caucasians and Chinese populations. India has a large population with multiple ethnic groups but there are no reports about the frequencies of these polymorphisms in north Indians. In the present study, we aimed to find out the allelic frequencies of CYP4F2 1347 G>A and GGCX 12970 C>G polymorphisms in a north Indian population and relate these to daily maintenance drug dose requirements of COA. Methods: CYP4F2 1347 G>A and GGCX 12970 C>G polymorphisms were genotyped by polymerase chain reaction -- restriction fragment length polymorphism (PCR-RFLP) protocols and Taqman SNP discrimination assays in healthy volunteers (n=102) and patients (n=225) receiving acenocoumarol, an oral anticoagulant, after cardiac valve replacement surgery. Results: In healthy volunteers, the allele frequencies for CYP4F2 1347 G>A and GGCX 12970 C>G were 43.14 and 1.43 per cent, respectively. No significant differences in mean weight normalized doses of acenocoumarol were found for these CYP4F2 and GGCX genotypes. Binary logistic regression analysis revealed no significant association of any of the genotypes or alleles with the dosing phenotypes for both the SNPs. Interpretation & conclusions: We report distinct frequencies of CYP4F2 1347 G>A and GGCX 12970 C>G polymorphisms in north Indians but these polymorphisms did not have significant bearing on maintenance dose of acenocoumarol oral anticoagulant in cardiac valve replacement patients. [ABSTRACT FROM AUTHOR]
- Published
- 2014
33. Candidate gene studies in gallbladder cancer: A systematic review and meta-analysis
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Srivastava, Kshitij, Srivastava, Anvesha, Sharma, Kiran Lata, and Mittal, Balraj
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GALLBLADDER cancer , *DISEASE incidence , *SYSTEMATIC reviews , *META-analysis , *EPIDEMIOLOGY of cancer , *CANCER genetics , *GENETICS of disease susceptibility , *GENETIC polymorphisms - Abstract
Abstract: Gallbladder cancer (GBC) is the most frequent biliary tract malignancy. Wide variations in GBC incidence and familial and epidemiological data suggest involvement of a genetic component in its etiopathogenesis. A systematic review of genetic association studies in GBC was performed by applying a meta-analysis approach and systematically reviewing PubMed database using appropriate terms. Odds ratios (ORs) and 95% confidence intervals (CIs) were appropriately derived for each gene–disease association using fixed and random effect models. Meta-regression with population size and genotyping method was also performed. Study quality was assessed using a 10-point scoring system designed from published guidelines. Following a review of 44 published manuscripts and one unpublished report, 80 candidate gene variants and 173 polymorphisms were analyzed among 1046 cases and 2310 controls. Majority of studies were of intermediate quality. Four polymorphisms with >3 separate studies were included in the meta-analysis [OGG1 (rs1052133), TP53 (rs1042522), CYP1A1 (rs1048943) and GSTM1 null polymorphism]. The meta-analysis demonstrated no significant associations of any of the above polymorphisms with GBC susceptibility except TP53 (rs1042522) polymorphism. To conclude, existing candidate gene studies in GBC susceptibility have so far been insufficient to confirm any association. Future research should focus on a more comprehensive approach utilizing potential gene–gene, gene–environment interactions and high-risk haplotypes. [Copyright &y& Elsevier]
- Published
- 2011
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34. Potential role of GABAA receptor subunit; GABRA6, GABRB2 and GABRR2 gene polymorphisms in epilepsy susceptibility and pharmacotherapy in North Indian population
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Kumari, Ritu, Lakhan, Ram, Kalita, J., Garg, R.K., Misra, U.K., and Mittal, Balraj
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GENETIC polymorphisms , *EPILEPSY , *DISEASE susceptibility , *DRUG therapy , *DRUG resistance , *ANTICONVULSANTS - Abstract
Abstract: Background: GABAA receptors influence the susceptibility to seizures, and variations in the receptor genes can contribute to antiepileptic drug resistance also. Methods: We investigated the possible associations of single nucleotide polymorphisms (SNPs) present in GABRA6 c. 1512 T>C, GABRB2 c. 1412 C>T, and GABRR2 c. IVS2C>G genes of GABAA receptors in epilepsy susceptibility and drug resistance in northern Indian patients with epilepsy. After screening a total of 202 healthy controls and 401 epilepsy patients were enrolled in study. The genotyping was done by PCR-RFLP methods. Results: The GABRA6 c. 1512 T>C, polymorphism was conferring risk for epilepsy susceptibility for TC (P=0.018), CC (P=0.0001) genotype and for C allele (P=0.0002). Another polymorphism GABRB2 c. 1412 C>T was also conferring high risk for epilepsy susceptibility CT (P=0.012), TT (P=0.778) genotype and for variant T allele (P=0.034) but was not associated with drug resistance. No association was found with epilepsy susceptibility or with drug resistance in case of GABRR2 c. IVS2C>G gene polymorphism. Conclusion: Overall, our findings suggest significant involvement of alpha (GABRA6) and beta (GABRB2) subunits of GABAA receptor in epilepsy susceptibility in north Indian population. [Copyright &y& Elsevier]
- Published
- 2011
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35. Frequencies of VKORC1 -1639 G>A, CYP2C9*2 and CYP2C9*3 genetic variants in the Northern Indian population.
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Rathore, Saurabh S., Agarwal, Surendra K., Pande, Shantanu, Mittal, Tulika, and Mittal, Balraj
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GENE frequency , *GENETIC polymorphisms , *ANTICOAGULANTS , *VITAMIN K , *HUMAN genetic variation , *POLYMERASE chain reaction , *ETHNIC groups - Abstract
Dose requirements for oral anticoagulants in thromboembolic events are influenced by polymorphisms in VKORC1 and CYP2C9 genes. The Indian population comprises multiple ethnic groups but no data is available on allele frequencies of these genes for North Indians. The present study aimed at establishing the allele and genotype frequencies of VKORC1 -1639 G>A, CYP2C9*2 and CYP2C9*3 alleles in the North Indian population. One hundred and two healthy subjects from the Northern Indian region were genotyped for VKORC1 -1639 G>A, CYP2C9*2 and CYP2C9*3 by polymerase chain reaction and restriction fragment length polymorphism. Allele frequencies were compared with that of the HapMap populations. The allele frequencies for VKORC1 -1639 A, CYP2C9*2 and CYP2C9*3 were found to be 14.22%, 4.90% and 3.92% respectively. This report also describes the inter-ethnic differences in the Northern Indian frequencies of VKORC1 -1639 G>A, CYP2C9*2 and CYP2C9*3 alleles with that of other populations and HapMap project data. VKORC1 -1639 G>A allele is present at moderately high frequency in the Northern Indian population. The frequencies of CYP2C9*2 and CYP2C9*3 alleles are also found to be different from other populations. [ABSTRACT FROM AUTHOR]
- Published
- 2010
36. Organic anion transporter protein (OATP1B1) encoded by SLCO1B1 gene polymorphism (388A>G) & susceptibility in gallstone disease.
- Author
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Jindal, Charulata, Kumar, Sandeep, Choudhari, Gourdas, Goel, Himanshu, and Mittal, Balraj
- Subjects
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ANIONS , *CARRIER proteins , *GENETIC polymorphisms , *ENTEROHEPATIC circulation , *GALLSTONES , *DISEASE susceptibility - Abstract
Background & objectives: Organic anion transport protein 1B1 (OATP1B1) is a major transporter protein for bile salt uptake in the enterohepatic circulation of bile salts. As the role of SLCO1B1 gene (encodes OATP1B1 or liver specific transporter-1) 388 A>G polymorphism in susceptibility towards gallstone disease is unclear the prevalence of this polymorphism in healthy north Indian population was investigated. Methods: Peripheral venous blood of 270 unrelated northern Indian patients with symptomatic gallstone disease and 270 unrelated healthy control subjects was screened for SLCO1B1 gene 388 A>G polymorphism by PCR-RFLP method and genotyping was done on 12 per cent polyacrylamide gel. The cross-sectional data on accrual of cases and controls were collected and odds ratio with 95 per cent CI calculated as for case-control design. Results: Allele frequencies of 388 G were 45 per cent in gallstone cases and 44 per cent in controls with no statistical significance. Genotype frequencies in gallstone cases and controls for, genotype AA were 30 and 32 per cent; AG: 51 and 47 per cent and GG: 16 and 21 per cent respectively. No significant association of any allele or genotype with gallstone disease was found. Interpretation & conclusions: Although the prevalence of SLCO1B1 gene 388A>G polymorphism in north Indian population in high, yet this polymorphism does not appear to play a significant role in susceptibility to gallstone formation. [ABSTRACT FROM AUTHOR]
- Published
- 2009
37. Microsomal epoxide hydrolase (EPHX1), slow (exon 3, 113His) and fast (exon 4, 139Arg) alleles confer susceptibility to squamous cell esophageal cancer
- Author
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Jain, Meenu, Tilak, Anup Raj, Upadhyay, Rohit, Kumar, Ashwani, and Mittal, Balraj
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ESOPHAGEAL cancer , *HYDROLASES , *SQUAMOUS cell carcinoma , *GENETIC polymorphisms - Abstract
Abstract: Genetic polymorphisms in xenobiotic metabolizing enzymes may alter risk of various cancers. Present case-control study evaluated the influence of EPHX1 genetic variations on squamous cell esophageal cancer (ESCC) susceptibility in 107 patients and 320 controls. EPHX1 polymorphic alleles were genotyped by direct sequencing (exon 3, Tyr113His) or PCR-RFLP (exon 4, His139Arg). Patients with exon 3 genotypes (Tyr113His, His113His) and 113His allele were at risk of ESCC (OR Tyr113His 2.0, 95% CI=1.2–3.4, p =0.007; OR His113His 2.3 95% CI=1.0–5.2, p =0.03 and OR His 1.5, 95% CI=1.0–2.1, p =0.01). In contrast, individuals with exon 4, 139Arg allele were at low risk of cancer (OR 0.34, 95% CI=0.20–0.56, p =0.001). However, none of haplotype combinations of exon 3 (Tyr113His) and exon 4 (His139Arg) polymorphisms showed modulation of risk for ESCC. Sub-grouping of patients based on anatomical location of tumor predicted that patients with exon 3, His113His and Tyr113His genotypes were at higher risk for developing ESCC tumor at upper and middle third locations (OR 4.4, 95% CI=1.0–18.5, p =0.04; OR 2.5, 95% CI=1.3–5.0, p =0.005 respectively). The frequency of exon 4, His139Arg genotype was significantly lower in ESCC patients with lower third tumor location as compared to controls (14.8% vs. 36.3%, p =0.02). In case-only study, gene-environment interaction of EPHX1 genotypes with tobacco, alcohol and occupational exposures did not appear to modulate the cancer susceptibility. In conclusion, exon 3, Tyr113His genotype was associated with higher risk of ESCC particularly at upper and middle-third anatomical locations of tumor. However, His139Arg genotype of exon 4, exhibited low risk for ESCC as well as its clinical characteristics. [Copyright &y& Elsevier]
- Published
- 2008
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38. Genetic susceptibility of epidermal growth factor +61A>G and transforming growth factor β1 -509C>T gene polymorphisms with gallbladder cancer
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Vishnoi, Monika, Pandey, Sachchida Nand, Modi, Dinesh Raj, Kumar, Ashok, and Mittal, Balraj
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CYTOKINES , *PEPTIDES , *CANCER patients , *GALLSTONES - Abstract
Summary: Epidermal growth factor (EGF) and transforming growth factor β1 (TGFβ1) play important roles in tumor biology. Single nucleotide polymorphisms in EGF and TGFB1 genes alter the expression of these growth factors and influence the tumorigenesis process. The aim of our present study was to determine the association of EGF+61A>G (rs4444903) and TGFB1-509C>T (rs1800469) gene polymorphism with susceptibility to gallbladder cancer (GBC). The present case–control association study was carried out in 126 confirmed GBC patients and 190 healthy subjects. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism methods. The GG genotype of EGF+61A>G was significantly associated with GBC [p = 0.012, odds ratio (OR) = 2.22, 95% confidence interval (CI) = 1.19–4.15] in comparison to healthy subjects. Analysis based on gender indicated risk due to GG genotype was limited to female GBC patients (p = 0.003, OR = 3.45, 95% CI = 1.52–7.82). Upon stratification of GBC patients on the basis of the presence or absence of gallstones, the risk due to EGF polymorphism was not modulated by the status of gallstones. The TGFB1-509C>T polymorphism was not associated with GBC. Also, we did not find any association of this polymorphism when GBC patients were subdivided on the basis of gender. However, after stratification of GBC patients on the status of gallstones, we determined that the CT genotype of TGFB1 was associated with increased risk of GBC without gallstones (p value = 0.030, OR = 2.90, 95% CI = 1.26–6.69). Furthermore, the combination of the GG genotype of EGF and the CT genotype of TGFB1 demonstrated synergistic increase in risk of GBC.In conclusion, the higher producing +61G allele of EGF and -509 CT genotype of TGFB1 synergistically increase the susceptibility of gallbladder cancer (p value = 0.003). Further study in large samples size is required to confirm our findings. [Copyright &y& Elsevier]
- Published
- 2008
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39. Role of genetic variant A-204C of cholesterol 7α-hydroxylase (CYP7A1) in susceptibility to gallbladder cancer
- Author
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Srivastava, Anvesha, Pandey, Sachchida Nand, Choudhuri, Gourdas, and Mittal, Balraj
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GENETIC polymorphisms , *BILIARY tract , *ISOPENTENOIDS - Abstract
Abstract: Gallbladder carcinoma (GBC) usually arises in the background of gallstone disease. Cholesterol 7α-hydroxylase (CYP7A1) is a rate-limiting enzyme for cholesterol catabolism and bile acid synthesis. A-204C genetic polymorphism in CYP7A1 may influence gene expression and thus affect the risk of gallstone disease and GBC. We aimed to study the association of A-204C variation of CYP7A1 gene promoter polymorphism in GBC patients, gallstone patients and healthy subjects. The study included 141 histopathologically proven GBC patients, ultrasonographically proven 185 symptomatic gallstone patients and 200 gallstone-free healthy subjects. Genotyping was done by PCR-RFLP method. CYP7A1 A-204C genotypes in control population were in Hardy–Weinberg equilibrium. The CC genotype conferred marginally significant risk for gallstone disease (p =0.051; OR=1.54; 95% CI=0.9–3.4). In GBC patients, the CYP7A1 A-204C polymorphism conferred high risk for GBC at genotype (p =0.005; OR=2.78; 95% CI: 1.3–5.6) as well as allele levels (p =0.008; OR=1.58 and 95% CI: 1.1–2.2). After stratification of GBC patients on the basis of presence or absence of gallstones, CC genotype imparted higher risk for GBC without stones (p =0.002; OR=4.44: 95% CI=1.7–11.3). The association of the polymorphism with GBC was more pronounced in female GBC patients, and also in cancer patients who developed GBC at advanced age. The CC genotype of CYP7A1 is an independent genetic risk factor for GBC but plays a modest role in susceptibility to gallstone disease. The GBC pathogenesis by CYP7A1 polymorphism appears to be independent of gallstone pathway and probably involves genotoxicity due to lipid peroxidation mechanisms. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
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40. Association of Toll-like receptor–4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions
- Author
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Achyut, B.R., Ghoshal, Uday C., Moorchung, Nikhil, and Mittal, Balraj
- Subjects
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GASTRITIS , *GENETIC polymorphisms , *GASTROENTERITIS , *HELICOBACTER pylori - Abstract
Summary: A Toll-like receptor–4 (TLR-4) Asp299Gly and Thr399Ileu substitution reduces responsiveness to Helicobacter pylori (H. pylori) lipopolysaccharide. CagA+ strains of H. pylori are known to be associated with gastroduodenal diseases. Therefore we aimed to evaluate association of TLR-4 substitutions and CagA seropositivity with gastritis and precancerous lesions in a northern Indian population. After upper gastrointestinal endoscopy, 130 rapid urease test (RUT)–positive patients with nonulcer dyspepsia (NUD) were included. Patients with NUD were also screened for H. pylori infection using modified Giemsa staining and anti-CagA IgG enzyme-linked immunoabsorbent assay. All patients and 200 asymptomatic control subjects were genotyped for TLR-4 substitutions using polymerase chain reaction–restriction fragment length polymorphism. We observed that frequencies of TLR-4 Asp299Gly variants were comparable between patients and control subjects, and also between positive and negative groups of precancerous lesions in patients. Frequencies of TLR-4 399Ileu allele (8% vs 3%, p = 0.008) and Asp299-Ileu399 haplotype (6.5% vs 3%, p = 0.022) were higher in patients than in control subjects at risk for gastritis (OR = 2.6 and 2.5, respectively). TLR-4 399Ileu allele carriers had higher risk for plasma cell infiltration (p = 0.023, OR = 10.6) that led to atrophy (p = 0.028, OR = 4.2) and intestinal metaplasia (p = 0.009, OR = 4.7). CagA positivity was more frequently associated with lymphoid follicle formation (p = 0.033, OR = 2.53). In conclusion TLR-4 Thr399Ileu substitution may be a risk factor for gastritis and precancerous lesions. CagA positivity may be a risk factor for lymphoid follicle development but not for other precancerous lesions in a northern Indian population. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
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41. Null association of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility and prognosis of Esophageal cancer in north Indian population and meta-analysis
- Author
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Umar, Meenakshi, Upadhyay, Rohit, Kumar, Shaleen, Ghoshal, Uday Chand, and Mittal, Balraj
- Subjects
- *
ESOPHAGEAL cancer , *OXIDOREDUCTASE genetics , *GENETIC polymorphisms , *META-analysis , *PROGNOSIS ,CANCER susceptibility - Abstract
Abstract: Introduction: NAD(P)H:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2), involved in detoxification of environmental carcinogens and activation of chemotherapeutic agents, are supposed to play critical role in carcinogenesis. So, we aimed to investigate the association of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility and prognosis of Esophageal cancer (EC) in north Indian population. We also performed Meta analysis of published literatures on NQO1 609C>T polymorphism to systematically evaluate its association with EC. Methods: We genotyped NQO1 609C>T and NQO2 -3423G>A polymorphisms in 200 incident EC cases (including 150 follow-up cases) and 200 controls using PCR RFLP based methods. Binary logistic regression was applied for risk estimation, while Kaplan Meier and Cox regression tests were applied for survival analysis. All Meta analysis tests were performed using MIX 2.0 software. Results: The present study did not find any significant association of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility to EC or its clinical phenotypes (histopathology, tumor location or lymph node metastasis) or interactions with lifestyle risk factors (tobacco usage, smoking, alcohol habit and occupational exposures). Meta analysis of NQO1 polymorphism also indicated null association of the polymorphism with EC overall or with cancer cases stratified by tumor histopathology/ethnicity. Moreover, no prognostic implication of both polymorphisms was observed in EC. Conclusion: NQO1 609C>T and NQO2 -3423G>A polymorphisms do not seem to play any significant role in susceptibility or prognosis of EC in north Indian population and results of Meta-analysis further reinforces null association of NQO1 609C>T polymorphism with EC susceptibility. [Copyright &y& Elsevier]
- Published
- 2012
- Full Text
- View/download PDF
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