Showing papers by "Moinak Banerjee published in 2015"

Erratum to: Pathogenesis of intracranial aneurysm is mediated by proinflammatory cytokine TNFA and IFNG and through stochastic regulation of IL10 and TGFB1 by comorbid factors

Abstract: Intracranial aneurysm (IA) is often asymptomatic until the time of rupture resulting in subarachnoid hemorrhage (SAH).There is no precise biochemical or phenotype marker for diagnosis of aneurysm. Environmental risk factors that associate with IA can result in modifying the effect of inherited genetic factors and thereby increase the susceptibility to SAH. In addition subsequent to aneurismal rupture, the nature and quantum of inflammatory response might be critical for repair. Therefore, genetic liability to inflammatory response caused by polymorphisms in cytokine genes might be the common denominator for gene and environment in the development of aneurysm and complications associated with rupture. Functionally relevant polymorphisms in the pro- and anti-inflammatory cytokine genes IL-1 complex (IL1A, IL1B, and IL1RN), TNFA, IFNG, IL3, IL6, IL12B, IL1RN, TGFB1, IL4, and IL10] were screened in radiologically confirmed 220 IA patients and 250 controls from genetically stratified Malayalam-speaking Dravidian ethnic population of south India. Subgroup analyses with genetic and environmental variables were also carried out. Pro-inflammatory cytokines TNFA rs361525, IFNG rs2069718, and anti-inflammatory cytokine IL10 rs1800871 and rs1800872 were found to be significantly associated with IA, independent of epidemiological factors. TGFB1 rs1800469 polymorphism was observed to be associated with IA through co-modifying factors such as hypertension and gender. Functional prediction of all the associated SNPs of TNFA, IL10, and TGFB1 indicates their potential role in transcriptional regulation. Meta-analysis further reiterates that IL1 gene cluster and IL6 were not associated with IA. The study suggests that chronic exposure to inflammatory response mediated by genetic variants in pro-inflammatory cytokines TNFA and IFNG could be a primary event, while stochastic regulation of IL10 and TGFB1 response mediated by comorbid factors such as hypertension may augment the pathogenesis of IA through vascular matrix degradation. The implication and interaction of these genetic variants under a specific environmental background will help us identify the resultant phenotypic variation in the pathogenesis of intracranial aneurysm. Identifying genetic risk factors for inflammation might also help in understanding and addressing the posttraumatic complications following the aneurismal rupture.

Polymorphic variants of mismatch repair gene human MutS homologue-2 influence oral squamous cell carcinoma in a South Indian population

Abstract: Background: Oral cancer is the third most common cancer in India. It is a multifactorial disease. Cells with defective mismatch repair (MMR) mechanisms cannot correct genetic errors that occur during cellular replication, resulting in a reduction in the fidelity of DNA repair. The objective of this study is to investigate the role of polymorphic variants in MMR gene human MutS homolog-2 ( hMSH2) in oral squamous cell carcinoma (OSCC) and associated clinicopathological features in Malayalam speaking population from Kerala. Materials and Methods: Patients diagnosed with OSCC, without superimposed premalignant and other malignant conditions were selected for polymorphism screening of hMSH2 gene. Two single nucleotide polymorphisms (SNPs), rs2303428 ( hMSH2 -6C/T) located at −6 of the 3' splice acceptor site of exon 13 and rs61756463 ( hMSH2 471C/A) located in exon 3 of hMSH2 were selected based on their functional relevance. Results: Polymorphism screening of hMSH2 gene suggests that rs2303428 was associated with both allelic and genotypic combinations with OSCC. In allelic level, the T allele was associated ( P = 0.009) with OR of 2.86, whereas in genotypic level the TT genotype was found to be significantly associated ( P = 0.012). In silico prediction of functional implication of this SNP indicated altered transcriptional regulation with functional significance score of 0.176. Although assessing the intergroup comparison within OSCC patients for age (≤50 and >50), gender and histo-differentiation grading, we could not find any association with any of these variables. Conclusion: Certain polymorphic variants in the MMR gene hMSH2 can result in OSCC in Malayalam speaking south Indian population and could indicate defective repair mechanism or Microsatellite instability. Distribution of rs2303428 allele had clear ethnic distribution across world population.

Microsatellite instability in D2S123 flanking the hMSH2 gene in oral squamous cell carcinoma in South India

Abstract: Background: Oral cancer is the third most common cancer in India. It is a multifactorial disease. Cells with defective mismatch repair gene hMSH2 can result in genomic instability in oral squamous cell carcinoma (OSCC) tumors. The objective of this study was to investigate the incidence of microsatellite instability (MSI) flanking the hMSH2 in OSCC tumors and relate the MSI status with the mutation profile of hMSH2 in Malayalam speaking population from Kerala. Materials and Methods: Patients diagnosed with OSCC, without superimposed premalignant and other malignant conditions, were recruited for the study based on strict selection criteria. 37 subjects from Malayalam speaking ethnic background of Kerala in India were selected. Blood and carcinoma tissues from were obtained from each patient diagnosed with OSCC. Big adenine tract 26 (BAT26) and D2S123 microsatellite flanking the hMSH2 gene were assessed for their peak patterns in each patient's blood and tissue DNA to analyze MSI and loss of heterozygosity (LOH). Results: No MSI was observed in any of the patient at BAT26 loci. Though BAT26 is reported to be quasi monomorphic, but interestingly it was found to be polymorphic in one patient. In D2S123 loci microsatellite alterations (MA) were observed in 50% of the OSCC patients, which comprised of both LOH and MSI. MA was observed to be significantly increased in moderately differentiated OSCC tumors. These MSI and LOH were independent of clinicopathological characteristics and mutation profile of hMSH2. Conclusion: Higher incidence of MSI at D2S123 in OSCC tumors could be indicative of diagnostic significance. However, this needs to be validated further in increased sample size and across different ethnic population.