Browsing by Author "Banerjee, M"
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Item Dopamine D3 receptor Ser9Gly variant is associated with impulse control disorders in Parkinson's disease patients(Parkinsonism Relat Disord., 2016-12) Krishnamoorthy, S; Rajan, R; Banerjee, M; Kumar, H; Sarma, G; Krishnan, S; Sarma, S; Kishore, AIntroduction: Impulse control disorders (ICD) are reported to occur at variable frequencies in different ethnic groups. Genetic vulnerability is suspected to underlie the individual risk for ICD. We investigated whether the allelic variants of dopamine (DRD3), glutamate (GRIN2B) and serotonin (HTR2A) receptors are linked to ICD in Indian Parkinson’s disease (PD) patients. Methods: We conducted a prospective, case-control study which included PD patients (70 with ICD, 100 without ICD categorized after direct psychiatric interview of patient and caregiver) and 285 healthy controls. Single nucleotide polymorphism (SNP) variants of DRD3 p.S9G (rs6280), GRIN2B c.2664C>T (rs1806201) and HTR2A c.102T>C (rs6313) were genotyped. Results: Multivariate regression analysis revealed that DRD3 p.Ser9Gly (rs6280) heterozygous variant CT (OR ¼ 2.22, 95% CI: 1.03e4.86, p ¼ 0.041), higher daily Levodopa equivalent doses (LED) of drugs (for 100 mg LED, OR ¼ 1.14, 95% CI: 1.01e1.29, p ¼ 0.041), current dopamine agonist but not Levodopa use (OR ¼ 2.16, 95% CI: 1.03e4.55, p ¼ 0.042) and age of onset of motor symptoms under 50 years (OR 2.09, 95% CI: 1.05e4.18, p ¼ 0.035) were independently associated with ICD. Conclusion: DRD3 p.Ser9Gly (rs6280) CT genotype is associated with ICD in Indian PD patients and this association is novel. Enhanced D3 receptor affinity due to gain-of-function conferred by the glycine residues could impair reward-risk assessment in the mesolimbic system and contribute to development of impulsive behaviour, in carriers of this genotype.Item Failure to find association between febrile seizures and SCN1A rs3812718 polymorphism in south Indian patients with mesial temporal lobe epilepsy and hippocampal sclerosis(EPILEPSY RESEARCH, 2012) Balan, S; Vellichirammal, NN; Banerjee, M; Radhakrishnan, KWe compared the allele and genotype frequencies of SCN1A SNP rs3812718 between patients with MTLE-HS of south Indian ancestry with and without febrile seizures (FS) and with ethnically matched controls. While we observed no significant difference in allele and genotype frequencies of rs3812718 between MTLE-HS patients with and without FS, A allele and AA genotype were overrepresented in MTLE-HS patients when compared to controls. We conclude that in the population studied, although rs3812718 polymorphism increases the susceptibility to MTLE-HS, this is not by increasing the susceptibility to FS. (C) 2012 Elsevier B.V. All rights reserved.Item Genetic Association Analysis of ATP Binding Cassette Protein Family Reveals a Novel Association of ABCB1 Genetic Variants with Epilepsy Risk, but Not with Drug-Resistance(PLOS ONE, 2014) Balan, S; Bharathan, SP; Vellichiramal, NN; Sathyan, S; Joseph, V; Radhakrishnan, K; Banerjee, MEpilepsy constitutes a heterogeneous group of disorders that is characterized by recurrent unprovoked seizures due to widely different etiologies. Multidrug resistance remains a major issue in clinical epileptology, where one third of patients with epilepsy continue to have seizures. Role of efflux transporters in multidrug resistant epilepsy has been attributed to drug-resistant epilepsy although, with discrepant observation in genetic studies. These discrepancies could be attributed to variety of factors such as variable definition of the anti-epileptic drug (AED)-resistance, variable epilepsy phenotypes and ethnicities among the studies. In the present study we inquired the role of multidrug transporters ABCB1 and ABCG2 variants in determining AED-resistance and susceptibility to epilepsy in three well-characterized cohorts comprising of mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) (prototype for AED-resistant epilepsy); juvenile myoclonic epilepsy (JME) (prototype for AED-responsive epilepsy); and healthy non-epileptic controls, in 738 subjects of Malayalam speaking south Indian ancestry. ABCB1 and ABCG2 variants were not found to be associated with drug resistance when AED-resistant and AED-responsive cohorts were compared. However, a significant association was observed between ABCB1 (C3435T) rs1045642 and risk of having epilepsy (MTLE-HS and JME pooled cohort; genotypic p-value = 0.0002; allelic p-value = 0.004). This association was seen persistent with MTLE-HS (genotypic p-value = 0.0008; allelic p-value = 0.004) and also with JME (genotypic p-value = 0.01; allelic p-value = 0.05) cohort individually. In-silico functional prediction indicated that ABCB1 rs1045642 has a deleterious impact on protein coding function and in splicing regulation. We conclude that the ABCB1 and ABCG2 variants do not confer to AED-resistance in the study population. However, ABCB1 rs1045642 increases vulnerability to epilepsy with greater tendency for MTLE-HS in south Indian ancestry from Kerala.Item Lack of association of Lysyl oxidase (LOX) gene polymorphisms with intracranial aneurysm in a south Indian population(MOLECULAR BIOLOGY REPORTS, 2013) Sathyan, S; Koshy, L; Lekshmi, KRS; Easwer, HV; Premkumar, S; Alapatt, JP; Nair, S; Bhattacharya, RN; Banerjee, MIntracranial aneurysm (IA) accounts for 85 % of haemorrhagic stroke and is mainly caused due to weakening of arterial wall. Lysyl oxidase (LOX) is a cuproenzyme involved in cross linking structural proteins collagen and elastin, thus providing structural stability to artery. Using a case-control study design, we tested the hypothesis whether the variants in LOX gene flanking the two LD block, can increase risk of aSAH among South Indian patients, either independently, or by interacting with other risk factors of the disease. SNPs were genotyped by fluorescence-based competitive allele-specific PCR (KASPar) chemistry. We selected 200 radiologically confirmed aneurysmal cases and 235 ethnically and age and gender matched controls from the Dravidian Malayalam speaking population of South India. We observed marked interethnic differences in the genotype distribution of LOX variants when compared to Japanese and African populations. However, there was no significant association with any of the LOX variants with IA. This study also could not observe any significant role of LOX polymorphisms in influencing IA either directly or indirectly through its confounding factors such as hypertension and gender in South Indian population.Item Major vault protein (MVP) gene polymorphisms and drug resistance in mesial temporal lobe epilepsy with hippocampal sclerosis(Gene., 2013-07) Balan, S; Lekshmi, S; Radha, K; Sathyan, S; Vijai, J; Banerjee, M; Radhakrishnan, KItem Major vault protein (MVP) gene polymorphisms and drug resistance in mesial temporal lobe epilepsy with hippocampal sclerosis (vol 526, pg 449, 2013)(GENE, 2013) Balan, S; Radha, SK; Sathyan, S; Vijai, J; Banerjee, M; Radhakrishnan, KItem Pathogenesis of intracranial aneurysm is mediated by proinflammatory cytokine TNFA and IFNG and through stochastic regulation of IL10 and TGFB1 by comorbid factors(JOURNAL OF NEUROINFLAMMATION, 2015) Sathyan, S; Koshy, LV; Srinivas, L; Easwer, HV; Premkumar, S; Nair, S; Bhattacharya, RN; Alapatt, JP; Banerjee, MBackground: 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. Methods: 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. Results: 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. Conclusions: 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.Item Pathogenesis of intracranial aneurysm is mediated by proinflammatory cytokine TNFA and IFNG and through stochastic regulation of IL10 and TGFB1 by comorbid factors (vol 12, 135, 2015)(JOURNAL OF NEUROINFLAMMATION, 2015) Sathyan, S; Koshy, LV; Srinivas, L; Easwer, HV; Premkumar, S; Nair, S; Bhattacharya, RN; Alapatt, JP; Banerjee, MItem Pharmacogenetic evaluation of ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase polymorphisms in teratogenicity of anti-epileptic drugs in women with epilepsy(ANNALS OF INDIAN ACADEMY OF NEUROLOGY, 2014) Jose, M; Banerjee, M; Mathew, A; Bharadwaj, T; Vijayan, N; Thomas, SVAim: Pregnancy in women with epilepsy (WWE) who are on anti-epileptic drugs (AEDs) has two- to three-fold increased risk of fetal malformations. AEDs are mostly metabolized by Cyp2C9, Cyp2C19 and Cyp3A4 and transported by ABCB1. Patients on AED therapy can have folate deficiency. We hypothesize that the polymorphisms in ABCB1, Cyp2C9, Cyp2C19 and methylene tetrahydrofolate reductase (MTHFR) might result in differential expression resulting in differential drug transport, drug metabolism and folate metabolism, which in turn may contribute to the teratogenic impact of AEDs. Materials and Methods: The ABCB1, Cyp2C9, Cyp2C19 and MTHFR polymorphisms were genotyped for their role in teratogenic potential and the nature of teratogenecity in response to AED treatment in WWE. The allelic, genotypic associations were tested in 266 WWE comprising of 143 WWE who had given birth to babies with WWE-malformation (WWE-M) and 123 WWE who had normal offsprings (WWE-N). Results: In WWE-M, CC genotype of Ex07 139C/T was overrepresented (P = 0.0032) whereas the poor metabolizer allele FNx012 and FNx012 FNx012 genotype of CYP2C219 was significantly higher in comparison to WWE-N group (P = 0.007 and P = 0.005, respectively). All these observations were independent of the nature of malformation (cardiac vs. non cardiac malformations). Conclusion: Our study indicates the possibility that ABCB1 and Cyp2C19 may play a pivotal role in the AED induced teratogenesis, which is independent of nature of malformation. This is one of the first reports indicating the pharmacogenetic role of Cyp2C19 and ABCB1 in teratogenesis of AED in pregnant WWE.Item Risk Factors for Aneurysmal Subarachnoid Hemorrhage in an Indian Population(CEREBROVASCULAR DISEASES, 2010) Koshy, L; Easwer, HV; Premkumar, S; Alapatt, JP; Pillai, AM; Nair, S; Bhattacharya, RN; Banerjee, MBackground: Aneurysmal subarachnoid hemorrhage (aSAH) has a mortality rate as high as 50%. The prevalence of intracranial aneurysms from various parts of India varies from 0.75 to 10.3%, with higher numbers of cases being diagnosed due to the increasing age of the population and improvements in imaging techniques. However, little is known about the attributable risk factors of aSAH in the Indian population. Methods: Using a case-control study we estimated the risk of factors such as hypertension, cigarette smoking, alcohol consumption, diabetes mellitus and family history of aSAH in a South Indian population. The population-attributable risk ( PAR) of smoking, hypertension and alcohol use was estimated for the South Indian as well as for the general Indian population. Results: Our results showed that cigarette smoking ( OR, 3.59; p < 0.001) and a history of hypertension ( OR, 2.98; p < 0.001) were significant risk factors associated with aSAH. When patients were classified by gender, it was observed that being a smoker and having hypertension increased the risk for aSAH by nearly fourfold in men. Among women, hypertension and older age were significant risk factors. The PAR estimates indicated that smoking ( OR, 3.59; 95% CI, 2.13-6.06) and hypertension ( OR, 2.98; 95% CI, 1.73-5.12) are significant risk factors. Conclusions: Hypertension and smoking may be causal risk factors which might also modify the effect of genetic factors that could increase susceptibility to aSAH in the Indian population. Since these risk factors are amenable to effective modification, our findings will be useful for a gender-specific management of aSAH. Copyright (C) 2010 S. Karger AG, BaselItem Role of ABCB1 Variants on Postoperative Seizure Recurrence in Patients with AED-Resistant Temporal Lobe Epilepsy(NEUROLOGY, 2012) Balan, S; Sumitha, PB; Bharadwaj, T; Lekshmi, S; Sathyan, S; Radhakrishnan, K; Banerjee, MItem Role of endothelial nitric oxide synthase gene polymorphisms in predicting aneurysmal subarachnoid hemorrhage in South Indian patients(DISEASE MARKERS, 2008) Koshy, L; Easwer, HV; Neetha, NV; Natarajan, C; Bhattacharya, RN; Banerjee, MEndothelial nitric oxide synthase (eNOS) gene polymorphisms have been implicated as predisposing genetic factors that can predict aneurysmal subarachnoid hemorrhage (aSAH), but with controversial results from different populations. Using a case-control study design, we tested the hypothesis whether variants in eNOS gene can increase risk of aSAH among South Indian patients, either independently, or by interacting with other risk factors of the disease. We enrolled 122 patients, along with 224 ethnically matched controls. We screened the intron-4 27-bp VNTR, the promoter T-786C and the exon-7 G894T SNPs in the eNOS gene. We found marked interethnic differences in the genotype distribution of eNOS variants when comparing the South Indian population with the reported frequencies from Caucasian and Japanese populations. Genotype distributions in control and patient populations were found to be in Hardy-Weinberg equilibrium. In patients, the allele, genotype and estimated haplotype frequencies did not differ significantly from the controls. Multiple logistic regression indicated hypertension and smoking as risk factors for the disease, however the risk alleles did not have any interaction with these risk factors. Although the eNOS polymorphisms were not found to be a likely risk factor for aSAH, the role of factors such as ethnicity, gender, smoking and hypertension should be evaluated cautiously to understand the genotype to phenotype conversion.Item Role of Proliferating Cell Nuclear Antigen (PCNA) mutations in inducing microsatellite instability in gliomas(AMERICAN JOURNAL OF HUMAN GENETICS, 2003)