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Biswas A.,ICMR Virus Unit Kolkata | Panigrahi R.,Tulane University | Pal M.,University of Calcutta | De B.K.,Calcutta Medical College | And 5 more authors.
Journal of Clinical and Experimental Hepatology | Year: 2013

Background: Interleukin-1β (IL-1β) is an important member of the family of the proinflammatory cytokines that modulate outcome of hepatitis B virus (HBV) infection. Objectives: This study was designed to investigate the relationship between the polymorphic genotypes of the interleukin-1β (IL-1β) promoter region and the interleukin-1 receptor antagonist gene (IL-1RN) and disease outcome in HBV-infected individuals. Methods: DNA was extracted from 395 study subjects including HBV carriers with varying clinical presentations, as well as healthy controls and spontaneously recovered cases (SRC). Polymorphisms in IL-1β (at position -511) and IL-1RN (variable nucleotide tandem repeats, VNTR) were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR based assay respectively. Results: Among the study subjects, different IL-1β (at position -511) (CC, CT and TT) and IL-1RN (1/1, 1/2, 2/2 and 1/3) polymorphic genotypes were found at variable proportions. Logistic regression analysis revealed, no notable difference at the level of IL-1β promoter (P=0.244; OR=0.78; 95% CI=0.52-1.18) or IL-1RN genotype polymorphism (P=0.840; OR=1.03; 95% CI=0.78-1.36) among the HBV carriers and controls or SRC cases. Pairwise proportion testing showed, IL-1β -511 genotype CC was significantly higher among asymptomatic carriers (ASC) in comparison with liver cirrhosis (LC) patients (P value=0.028) and healthy control group (P-value=0.036). IL-1RN genotype 2/2 was considerably higher in LC group than SRC as well as control group. Combinations of IL-1β (-511) and IL-1RN polymorphisms were associated with disease progression, such as CC-1/2 with ASC and TT-2/2 with LC. Conclusion: IL-1β polymorphisms are found to be associated with disease severity. Different polymorphic combinations are associated with degree of disease severity. Overall this is the first report from Eastern India, which shows association of IL-1β polymorphisms with HBV-related hepatic complications. © 2013 INASL. Source

Panigrahi R.,ICMR Virus Unit Kolkata | Sarkar N.,ICMR Virus Unit Kolkata | Biswas A.,ICMR Virus Unit Kolkata | Pal A.,ICMR Virus Unit Kolkata | And 6 more authors.
Journal of Clinical and Experimental Hepatology | Year: 2014

Background: TNF-. α promoter polymorphism has been known to be a potential predictive factor in patients withHBV infection. We therefore tried to investigate whether the TNF-. α promoter polymorphism at position -238,-857 and -863 was associated with the outcome of HBV infection in a population from Orissa, southern part of East India. Methods: A total of 195 patients recruited for the study were classified into 85 controls and 110HBV infected cases, which included 34 IC, 30 CLD, 32 LC and 14 HCC patients. The polymorphisms at the respective sites were detected by a PCR-RFLP followed by statistical analysis. Results: The frequency of the genotype -238GG and the allele -238G in the cases (89.0% and 92.7% respectively) was significantly higher than that in the controls (68.2% and 82.2% respectively) (P<0.001, OR=3.8 and P=0.001, OR=2.73). Whereas the -238GA genotype was significantly high in the control group (28.2%) when compared to the cases (7.2%) (P<0.001, OR=0.2). Similarly, the frequency of -863CC and the allele -863C was significantly higher among the cases (24.5% and 49.5%) compared to controls (1.17% and 34.7%), (P<0.001, OR=27.32 and P=0.003, OR=1.85), whereas the -863CA genotype was significantly high in the controls (67.0%) when compared to the cases (50.0%) (P=0.01, OR=0.49). Haplotype -863C/-857C/-238G in cases was significantly higher than controls (P=0.002). Multivariate logistic regression analysis indicates that the genotype -863CC bears a negative association with liver disease progression. Conclusion: The present study established an association of polymorphisms at site -238 and -863 of the TNF-α promoter with the outcome HBV infection and disease progression. © 2014 INASL. Source

Panigrahi R.,ICMR Virus Unit Kolkata | Biswas A.,ICMR Virus Unit Kolkata | De B.K.,Calcutta Medical College | Chakrabarti S.,Indian National Institute of Cholera and Enteric Diseases | Chakravarty R.,ICMR Virus Unit Kolkata
Virology Journal | Year: 2013

Background: Antiviral therapy using nucleos(t)ide analogues (NAs) is an effective control measure of chronic hepatitis B virus (HBV) infection; however they need long term treatment. Presence of drug-resistance mutations may get in the way of the efficacy of antiviral therapy. Our study was aimed at defining the prevalence of HBV drug-resistance in HBVrt region in a population of 147 HBsAg positive patients. Findings. HBV/D has shown multiple types of HBVrt mutations both among treatment naïve (65.0%, 13 of 20 HBV/D) and treated patients (56.2%, 9 of 16 HBV/D). In additional, several mutations, with a suggested role in drug resistance, were detected among the treatment naïve as well as the treated patients. The mutations reported to be involved in reduction of drug effectiveness, was common among non-responders to therapy as well as among the naïve patients. Notably, classical antiviral resistance mutations (rtL80I/V-rtI169T-rtV173L-rtL180M-rtA181T/V/S-rtT184A/S/G/C-rtA194T- rtS202C /G/I -rtM204V/I-rtN236T-rtM250V) were not detected. Conclusion: The prevalence of putative NAr mutations among non responders to therapy suggests that they might have role in reduced efficacy of currently available antivirals and requires further investigations. © 2013 Panigrahi et al.; licensee BioMed Central Ltd. Source

Firdaus R.,ICMR Virus Unit Kolkata | Biswas A.,ICMR Virus Unit Kolkata | Saha K.,ICMR Virus Unit Kolkata | Mukherjee A.,ICMR Virus Unit Kolkata | And 5 more authors.
BioMed Research International | Year: 2014

Background. Hepatitis C virus is the major cause of chronic hepatitis worldwide which finally leads to the development of hepatocellular carcinoma. Toll like receptors (TLRs) play an important role in the course of many viral infections, but the role of TLRs in HCV pathogenesis has not been well elucidated so far. Objective. The aim of this study was to analyse the mRNA expression of TLRs 3, 7, and 8 in different stages of HCV infection including chronic, cirrhosis, interferon treated resolved, and relapsed cases. Methodology. Total RNA from whole blood was extracted and mRNA expression of TLRs 3, 7, and 8 genes was analyzed by quantitative real-time RT-PCR using β-Actin gene as an internal control. Results. This study consisted of 100 HCV infected individuals and twenty healthy controls. TLR 3 expression was found to be significantly elevated in individuals who had spontaneously cleared the virus (p < 0.001), whereas TLR 7 was found to be 3.26 times more elevated in patients with cirrhosis of liver. In IFN induced individuals, TLR 8 expression levels were found to be 2.28-fold elevated as compared to control population. Conclusion. TLRs 3, 7, and 8 are prime biomarker candidates for HCV infection mRNA expression analysis which might improve current therapeutic approaches. © 2014 Rushna Firdaus et al. Source

Mukherjee N.,Chittaranjan National Cancer Institute | Bhattacharya N.,Chittaranjan National Cancer Institute | Sinha S.,WVU Eye Institute | Alam N.,Chittaranjan National Cancer Institute | And 3 more authors.
International Journal of Biological Markers | Year: 2011

The adenomatous polyposis coli (APC) and mutated in colorectal cancer (MCC) genes are key regulatory genes of the Wnt/β-catenin signaling pathway, which are independently involved in maintaining low levels of β-catenin in the cell. In addition to genetic and epigenetic alterations, some genetic polymorphisms in the genes associated with the Wnt signaling pathway have been reported to be associated with an increased risk of cancer, including breast cancer. In the present study we analyzed the association of genotype and haplotype status of two single nucleotide polymorphisms (SNPs), rs2229992 and rs11283943, in the APC and MCC genes, respectively, with an increased risk of breast carcinogenesis in a breast cancer and control population from eastern India. We observed a signifcant association of the rs11283943 SNP with increased breast cancer risk. Two specifc haplotypes involving the minor allele of rs11283943 were found to be associated with an increased breast cancer risk. Kaplan-Meier curves showed a signifcant association of the 2-2 genotype (genotype homozygous for the rs11283943 minor allele) with decreased survival (p=0.045) of the breast cancer patients in our study, in particular patients with early-onset BC. © 2011 Wichtig Editore. Source

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