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INTRODUCTION: RNF213 mutations have been reported mostly in moyamoya disease (MMD) with varying frequencies across different ethnicities. However, its prevalence in non-MMD adult-onset ischemic stroke is still not well explored. AIMS AND OBJECTIVES: This present study thus aims to screen the most common RNF213 variant (Arg4810Lys, among East Asians) in the Eastern Indian non-MMD ischemic stroke patients and correlate it with long-term progression and prognosis of the patients. The subjects were analyzed for this variant using PCR-RFLP and confirmed using Sanger sequencing method. RESULT AND CONCLUSION: We have identified Arg4810Lys variant among eleven young-onset familial ischemic stroke patients in heterozygous manner. A positive correlation of the variant with positive family history (P = 0.001), earlier age at onset (P = 0.002), and history of recurrent stroke (P = 0.015) was observed. However, the carriers showed better cognitive performances in memory (P = 0.042) and executive function (P = 0.004). Therefore, we can conclude that Arg4810Lys/RNF213 - a pathogenic variant for young-onset familial ischemic stroke with higher incidence of recurrent events unlike in MMD cases, have no additional impact on cognition among Eastern Indians.
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AVC Isquêmico , Doença de Moyamoya , Adulto , Humanos , Doença de Moyamoya/epidemiologia , Predisposição Genética para Doença , Adenosina Trifosfatases/genética , Ubiquitina-Proteína Ligases/genética , Estudos de Associação Genética , Mutação/genéticaRESUMO
Alzheimer disease and Parkinson disease dementia are the 2 most common neurodegenerative diseases have substantial overlap in pathologic, genetic, and clinical manifestation and complex in nature. Here, for the first time, we report an Indian female young patient who presented with clinical manifestation of both Alzheimer disease and Parkinsonism, including dystonia with rapid disease progression. We identified a heterozygous mutation in the ATP-binding cassette transporter A7 gene and double heterozygous mutation in PRKN by whole-exome sequencing. This case is an example of complex etiology of neurodegenerative disorders and highlights the importance of genetic tests, including whole-exome sequencing in complex diseases.
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Doença de Alzheimer , Demência , Doença de Parkinson , Transtornos Parkinsonianos , Feminino , Humanos , Transportadores de Cassetes de Ligação de ATP/genética , Demência/genética , Sequenciamento do Exoma , Mutação/genética , Transtornos Parkinsonianos/genéticaRESUMO
Background & objectives: Parkinsonian disorder, including Parkinson's disease (PD), is an aetiologically complex neurodegenerative disorder. Mutations in leucine-rich repeat kinase 2 (LRRK2) gene have been implicated in an autosomal dominant form of PD with variable penetrance. The identification of a common LRRK2 variant (p.Gly2019Ser) in dementia with Lewy bodies indicated its potential role in Parkinsonian disorder. The current study was aimed to identify the p.Gly2019Ser variant in Indian patients with Parkinsonian disorder. Methods: The patient group consisting of 412 classical PD patients, 107 PD patients with cognitive impairment, 107 patients with Parkinson plus syndrome and 200 unrelated controls were recruited from eastern part of India. The allele representing p.Gly2019Ser variant was screened by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Results: The p.Gly2019Ser variant was identified in an East Indian young-onset female PD patient in a heterozygous state having several motor and autonomic problems without disturbed cognition. Her younger brother, sister and elder son harbouring the same mutation were asymptomatic carriers for the variant. However, the influence of DNM3 on decreased disease onset in this family was not clear. Interpretation & conclusions: Identification of the p.Gly2019Ser variant in only one patient among a large number of Indian patients (n=626) with Parkinsonian disorder in our study suggests a limited role of the LRRK2 variant towards disease pathogenesis.
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Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Doença de Parkinson , Adulto , Feminino , Predisposição Genética para Doença , História do Século XVI , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Mutação , Doença de Parkinson/epidemiologia , Doença de Parkinson/genética , PenetrânciaRESUMO
Bone cancer originates from bone and rapidly spreads to the rest of the body affecting the patient. A quick and preliminary diagnosis of bone cancer begins with the analysis of bone X-ray or MRI image. Compared to MRI, an X-ray image provides a low-cost diagnostic tool for diagnosis and visualization of bone cancer. In this paper, a novel technique for the assessment of cancer stage and grade in long bones based on X-ray image analysis has been proposed. Cancer-affected bone images usually appear with a variation in bone texture in the affected region. A fusion of different methodologies is used for the purpose of our analysis. In the proposed approach, we extract certain features from bone X-ray images and use support vector machine (SVM) to discriminate healthy and cancerous bones. A technique based on digital geometry is deployed for localizing cancer-affected regions. Characterization of the present stage and grade of the disease and identification of the underlying bone-destruction pattern are performed using a decision tree classifier. Furthermore, the method leads to the development of a computer-aided diagnostic tool that can readily be used by paramedics and doctors. Experimental results on a number of test cases reveal satisfactory diagnostic inferences when compared with ground truth known from clinical findings.
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Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Máquina de Vetores de Suporte , Humanos , Imageamento por Ressonância Magnética , Gradação de Tumores , Estadiamento de Neoplasias , Raios XRESUMO
INTRODUCTION: Levodopa-induced dyskinesia (LID) is a debilitating motor feature in a subset of patients with Parkinson's disease (PD) after prolonged therapeutic administration of levodopa. Preliminary animal and human studies are suggestive of a key role of dopamine type 3 (D3) receptor polymorphism (Ser9Gly; rs6280) in LID. Its contribution to development of LID among Indian PD patients has remained relatively unexplored and merits further investigation. METHODS AND MATERIALS: 200 well-characterised PD patients (100 without LID and 100 with LID) and 100 age-matched healthy controls were recruited from the outpatient department of Institute of Neurosciences Kolkata. MDS-UPDRS (Unified Parkinson's Disease Rating Scale from International Movement Disorder Society) Part III and AIMS (abnormal involuntary movement scale) were performed for estimation of severity of motor features and LID respectively in the ON state of the disease. Participants were analysed for the presence of Ser9Gly single nucleotide variant (SNV) (rs6280) by polymerase chain reaction followed by restriction fragment length polymorphism techniques. RESULTS: The frequency of AA genotype (serine type) was more frequently present in PD patients with LID compared to PD patients without LID (50 % vs 28 %; P = 0.002; OR = 2.57, 95 % CI: 1.43 - 4.62). The abnormal involuntary movement scale score was significantly higher in PD patients with AA genotype compared to carriers of glycine allele (AG + GG) (4.08 ± 3.35; P = 0.002). CONCLUSION: We observed a significant association of serine type SNV (rs6280) in D3 receptor gene in a cohort of PD patients with LID from India. More severe motor severity was found in patients with glycine substitution of the same SNV. The current study emphasised the role of D3 receptor in the pathogenesis of LID.
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Discinesia Induzida por Medicamentos , Doença de Parkinson , Animais , Humanos , Antiparkinsonianos/uso terapêutico , Discinesia Induzida por Medicamentos/genética , Discinesia Induzida por Medicamentos/tratamento farmacológico , Glicina , Levodopa/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D3/genética , Serina/genéticaRESUMO
Rapid depletion of groundwater and climate change mediated shifting precipitation pattern is forcing farmers to look for alternative irrigation options like wastewater. However, routine irrigation with trace metal contaminated wastewaters could potentially pollute soil as well as cause health risks through the consumption of food products grown in contaminated soil. Thus, the present study aimed to investigate the trace metals build-up status in topsoil and potato (Solanum tuberosum L.) tubers upon continuous irrigation with coalmine effluent contaminated wastewater compared to irrigation with groundwater and surface water over three consecutive years. Soil pollution status and human health risk associated with consumption of potato tubers grown on wastewater-irrigated soil was also assessed in this study. Three separate experimental sites differing in irrigation source (groundwater, surface water, and coalmine wastewater) were selected near Barapukuria Coal Mining Company Limited located at Parbatipur upazilla of Dinajpur district, Bangladesh. Nine trace metals namely arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) were estimated. Results showed significantly higher trace metal content in both soil and potato tubers due to wastewater irrigation. Wastewater suitability for irrigation regarding Cd, Cr, Cu, Fe, Ni and Pb were off the permissible level although the soil contamination with trace metals and their levels in potato tubers remained within the safety limit. Health risk assessment revealed that, consumption of potato tubers grown in wastewater-irrigated soil remained safe although health risk associated with Cr was almost at the border. The study exclusively highlighted the core massage that, trace metal contamination of both soil and potatoes cultivated in them was increasing alarmingly due to three years of wastewater-irrigation. Although the extent of contamination was below critical limit, it can potentially become hazardous in years to come unless wastewater-irrigation is checked. This study was successful to provide valuable insights regarding the potential environmental and human health threats that might arise due to unmindful irrigation of contaminated coalmine wastewater. Besides, this study should prove useful in strategizing safety measures for cropping under trace metal contaminated soils and for planning industrial effluent disposal to avoid agricultural soil contamination.
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The wide tunability of the energy bandgap of colloidal lead sulfide (PbS) quantum dots (QDs) has uniquely positioned them for the development of single junction and tandem solar cells. While there have been substantial advancements in moderate and narrow bandgap PbS QDs-ideal for single junction solar cells and the bottom cell in tandem solar cells, respectively; progress has been limited in high-bandgap PbS QDs that are ideally suited for the formation of the top cell in tandem solar cells. The development of appropriate high bandgap PbS QDs would be a major advancement toward realizing efficient all-QD tandem solar cells utilizing different sizes of PbS QDs. Here, we report a comprehensive approach encompassing synthetic strategy, ligand engineering, and hole transport layer (HTL) modification to implement high-bandgap PbS QDs into solar cell devices. We achieved a greater degree of size homogeneity in high-bandgap PbS QDs through the use of a growth retarding agent and a partial passivation strategy. By adjusting the ligand polarity, we successfully grow HTL over the QD film to fabricate solar cells. With the aid of an interface modifying layer, we incorporated an organic HTL for the realization of high-performance solar cells. These solar cells exhibited an impressive open-circuit voltage of 0.824 V and a power conversion efficiency of 10.7%, marking a 360% improvement over previous results.
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In our pursuit of high-power terahertz (THz) wave generation, we propose innovative edge-terminated single-drift region (SDR) multi-quantum well (MQW) impact avalanche transit time (IMPATT) structures based on the AlxGa1-xN/GaN/AlxGa1-xN material system, with a fixed aluminum mole fraction of x = 0.3. Two distinct MQW diode configurations, namely p+-n junction-based and Schottky barrier diode structures, were investigated for their THz potential. To enhance reverse breakdown characteristics, we propose employing mesa etching and nitrogen ion implantation for edge termination, mitigating issues related to premature and soft breakdown. The THz performance is comprehensively evaluated through steady-state and high-frequency characterizations using a self-consistent quantum drift-diffusion (SCQDD) model. Our proposed Al0.3Ga0.7N/GaN/Al0.3Ga0.7N MQW diodes, as well as GaN-based single-drift region (SDR) and 3C-SiC/Si/3C-SiC MQW-based double-drift region (DDR) IMPATT diodes, are simulated. The Schottky barrier in the proposed diodes significantly reduces device series resistance, enhancing peak continuous wave power output to approximately 300 mW and DC to THz conversion efficiency to nearly 13% at 1.0 THz. Noise performance analysis reveals that MQW structures within the avalanche zone mitigate noise and improve overall performance. Benchmarking against state-of-the-art THz sources establishes the superiority of our proposed THz sources, highlighting their potential for advancing THz technology and its applications.
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Movement disorder (MD) is an important branch of neurology and has great potentiality in management because of improved diagnosis and therapeutic strategies. Over the last three decades, emphasis has been laid on the evaluation of various MDs in India by a limited number of interested neurologists and basic scientists. In this review, we want to highlight common problems of MDs in India with regard to epidemiology, clinical features and genetics.
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Transtornos dos Movimentos/diagnóstico , Gerenciamento Clínico , Humanos , Índia/epidemiologia , Transtornos dos Movimentos/epidemiologia , Transtornos dos Movimentos/genética , Prevalência , Fatores de Risco , Taxa de SobrevidaRESUMO
Diffuse Correlation Spectroscopy (DCS) is a widely used non-invasive measurement technique to quantitatively measure deep tissue blood flow. Conventional implementations of DCS use expensive single photon counters as detecting elements and optical probes with bulky fiber optic cables. In recent years, newer approaches to blood flow measurement such as Diffuse Speckle Contrast Analysis (DSCA) and Speckle Contrast Optical Spectroscopy (SCOS), have adapted speckle contrast analysis methods to simplify deep tissue blood flow measurements using cameras and single photon counting avalanche detector arrays as detectors. Here, we introduce and demonstrate integrated Diffuse Speckle Contrast Spectroscopy (iDSCS), a novel optical sensor setup which leverages diffuse speckle contrast analysis for probe-level quantitative measurement of tissue blood flow. iDSCS uses a standard photodiode configured in photovoltaic mode to integrate photon intensity fluctuations over multiple integration durations using a custom electronic circuit, as opposed to the high frequency sampling of photon counts with DCS. We show that the iDSCS device is sensitive to deep-tissue blood flow measurements with experiments on a human forearm and compare the sensitivity and dynamic range of the device to a conventional DCS instrument. The iDSCS device features a low-cost, low-power, small form factor instrument design that will enable wireless probe-level measurements of deep tissue blood flow.
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Sugarcane (Saccharum officinarum L.), a globally cultivated carbohydrate producing crop of industrial importance is being challenged by soil salinity due to its glycophytic nature. Water stress coupled with cellular and metabolic alterations resulting from excess sodium (Na+) ion accumulation is irreversibly damaging during early crop developmental stages that often results in complete crop failure. This study therefore aimed to explore the potential of salicylic acid as a sett priming material to mitigate the negative effects of salt stress on sugarcane during germination and early growth stages. Five doses of salicylic acid (0 [hydropriming] [control], 0.5 mM, 1 mM, 1.5 mM and 2 mM) were tested against three levels of salinity (0.5 dS m-1 [control], 4 dS m-1, and 8 dS m-1) within a polyhouse environment. Results revealed 11.2%, 18.5%, 25.4%, and 38.6%, average increase in final germination, germination energy, seedling length and seedling vigor index respectively with a subsequent reduction of 21% mean germination time. Investigations during early seedling growth revealed 21.6%, 17.5%, 27.0%, 39.9%, 10.7%, 11.5%, 17.5%, 47.9%, 35.3% and 20.5% overall increase in plant height, total leaf area, shoot dry matter, root dry matter, leaf greenness, relative water content, membrane stability index, proline content, total antioxidant activity and potassium (K+) ion accumulation respectively with a subsequent reduction of 24.9% Na+ ion accumulation and 35.8% Na+/K+ ratio due to salicylic acid priming. Germination, seedling growth and recovery of physiochemical traits were highly satisfactory in primed setts than non-primed ones even under 8 dS m-1 salinity level. This study should provide useful information for strategizing salinity management approaches for better productivity of sugarcane.
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Post-stroke cognitive impairment (PSCI) is a clinical outcome in around 30% of post-stroke survivors. BDNF is a major gene in this regard. It is regulated by circadian rhythm. The circadian genes are correlated with stroke timings at molecular level. However, studies suggesting the role of these on susceptibility to PSCI are limited. We aim here to determine: (a) genetic risk variants in circadian clock genes, BDNF and (b) dysregulation in expression level of CLOCK, BMAL1, and BDNF that may be associated with PSCI. BDNF (rs6265G/A, rs56164415C/T), CLOCK (rs1801260T/C, rs4580704G/C), and CRY2 (rs2292912C/G) genes variants were genotyped among 119 post-stroke survivors and 292 controls from Eastern part of India. In addition, we analyzed their gene expression in Peripheral blood Mononuclear cells (PBMC) from 15 PSCI cases and 12 controls. The mRNA data for BDNF was further validated by its plasma level through ELISA (n = 38). Among the studied variants, only rs4580704/CLOCK showed an overall association with PSCI (P = 0.001) and lower Bengali Mini-Mental State Examination (BMSE) score. Its 'C' allele showed a correlation with attention deficiency. The language and memory impairments showed association with rs6265/BDNF, while the 'CC' genotype of rs2292912/CRY2 negatively influenced language and executive function. A significant decrease in gene expression for CLOCK and BDNF in PBMC (influenced by specific genotypes) of PSCI patients was observed than controls. Unlike Pro-BDNF, plasma-level mBDNF was also lower in them. Our results suggest the genetic variants in CLOCK, CRY2, and BDNF as risk factors for PSCI among eastern Indians. At the same time, a lowering expression of CLOCK and BDNF genes in PSCI patients than controls describes their transcriptional dysregulation as underlying mechanism for post-stroke cognitive decline.
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Disfunção Cognitiva , Acidente Vascular Cerebral , Humanos , Leucócitos Mononucleares , Fator Neurotrófico Derivado do Encéfalo/genética , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/genética , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/genética , Fatores de Risco , Variação GenéticaRESUMO
The aim of this study is to examine the role of GCH1 among Indians affected with dopa responsive dystonia (DRD) and early onset Parkinson's disease (EOPD). The patients (n = 76 including 19 DRD and 36 EOPD) and controls (n = 138) were screened for variants in GCH1 by PCR amplification of exons, splice junctions and 1 kb upstream region followed by SSCP and DNA sequencing. Four novel variants (p.Met1Val, p.Val204_205del, IVS3+68A>G, and IVS5-6T>G) were identified in 10 patients but not in the controls. In addition to two nonsynonymous changes, identified in four DRD patients in heterozygous condition, one intronic variant (IVS5-6T>G) could be linked to pathogenesis of the disease since it has the potential of altering the splice site as assessed by in silico analysis. Patients carrying different nonsynonymous variants had remarkable variation in clinical phenotype. Consistent with earlier reports, severity of clinical phenotype and the age of onset varied among family members harboring the same mutation. No mutation was detected in the EOPD patients. Three novel mutations in GCH1 gene have been found and are shown to be associated with variable clinical phenotypes mostly within the spectrum of DRD. The mutations identified represent 15.79% (3/19) of east Indian DRD patient cohort.
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Distonia/genética , GTP Cicloidrolase/genética , Predisposição Genética para Doença/genética , Mutação/genética , Adulto , Povo Asiático/genética , Análise Mutacional de DNA , Dopaminérgicos/uso terapêutico , Distonia/tratamento farmacológico , Saúde da Família , Feminino , Humanos , Índia , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/genéticaRESUMO
Diffuse Correlation Spectroscopy (DCS), a noninvasive optical technique, measures deep tissue blood flow using avalanche photon counting modules and data acquisition devices such as FPGAs or correlator boards. Conventional DCS instruments use in-processor counter modules that consume 32 bits/channel which is inefficient for low-photon budget situations prevalent in diffuse optics. Scaling these photon counters for large-scale imaging applications is difficult due to bandwidth and processing time considerations. Here, we introduce a new, lossless compressed sensing approach for fast and efficient detection of photon counts. The compressed DCS method uses an array of binary-coded-decimal counters to record photon counts from 8 channels simultaneously as a single 32-bit number. We validate the compressed DCS approach by comparisons with conventional DCS in experiments on tissue simulating phantoms and in-vivo arm cuff occlusion. Lossless compressed DCS was implemented with 87.5% compression efficiency. In tissue simulating phantoms, it was able to accurately estimate a tissue blood flow index, with no statistically significant difference compared to conventional DCS. Compressed DCS also recorded blood flow in vivo, in human forearm, with signal-to-noise ratio and dynamic range comparable to conventional DCS. Lossless 87.5% efficient compressed sensing counting of photon counts meets and exceeds benchmarks set by conventional DCS systems, offering a low-cost alternative for fast (~100 Hz) deep tissue blood flow measurement with optics.
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Diffuse correlation spectroscopy (DCS), a popular optical technique for fast noninvasive measurement of blood flow, is commonly implemented using expensive fiber-coupled long coherence length laser systems. Here, we report the development of a portable and fiber-less approach that can be used as a low-cost alternative to illuminate tissue in DCS instruments. We validate the accuracy and noise characteristics of the fiber-less DCS laser source, by comparisons against traditional DCS light sources, with experiments on controlled tissue-simulating phantoms and in humans.
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BACKGROUND: Parkinson's disease (PD) is a multifaceted illness affecting ~ 0.3% of the world population. The genetic complexity of PD has not been, fully elucidated. Several studies suggest that mitochondrial DNA variants are associated with PD. OBJECTIVE: Here, we have explored the possibility of genetic association between mitochondrial haplogroups as well as three independent SNPs with PD in a representative east Indian population. METHODS AND MATERIAL: The Asian mtDNA haplogroups: M, N, R, B, D, M7, and 3 other SNPs: 4336 T/C, 9055 G/A, 13708 G/A were genotyped in 100 sporadic PD patients and 100 matched controls via conventional PCR-RFLP-sequencing approach. RESULTS: The distribution of mtDNA haplogroups, as well as 3 single polymorphisms, did not show any significant differences (P > 0.05) between patients and controls. CONCLUSION: This is the first of its kind of study from India that suggests no association of selected mitochondrial DNA variations with PD.
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DNA Mitocondrial , Doença de Parkinson , Povo Asiático , DNA Mitocondrial/genética , Genótipo , Haplótipos , Humanos , Índia , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
To fight against the present pandemic scenario of COVID-19 outbreak, medication with drugs and vaccines is extremely essential other than ventilation support. In this paper, we present a list of ligands which are expected to have the highest binding affinity with the S-glycoprotein of 2019-nCoV and thus can be used to make the drug for the novel coronavirus. Here, we implemented an architecture using 1D convolutional networks to predict drug-target interaction (DTI) values. The network was trained on the KIBA (Kinase Inhibitor Bioactivity) dataset. With this network, we predicted the KIBA scores (which gives a measure of binding affinity) of a list of ligands against the S-glycoprotein of 2019-nCoV. Based on these KIBA scores, we are proposing a list of ligands (33 top ligands based on best interactions) which have a high binding affinity with the S-glycoprotein of 2019-nCoV and thus can be used for the formation of drugs.
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INTRODUCTION: GBA mutations have been reported in PD, PDD and DLB - but not associated with cognitive impairment for example in PSP, AD or MSA. However, frequencies of GBA mutations are ethnicity dependent. The present study aims to identify commonly reported GBA mutations (mostly from Asia), among eastern Indian patients with neurodegenerative disorders. METHODS: The patient cohort consisting of 198 classical PD cases, 136 PD cases with cognitive impairment, 184 cases with Parkinson Plus syndrome, 46 AD and 241 unrelated controls, from eastern India. Subjects were analyzed for IVS2 + 1A > G, p.Arg120Trp, p.His255Gln, p.Arg257Gln, p.Glu326Lys, p.Asn370Ser, p.Asp409His, p.Leu444Pro, & RecNciI by PCR-RFLP techniques and confirmed by Sanger sequencing method. RESULTS: We have identified only p.Leu444Pro variant among nine cases; three PDD, one DLB, two PD, two PSP and one AD patients in heterozygous condition. The highest frequency for p.Leu444Pro variant was found among PDD subgroup (3.95 %, P = 0.0134). An overall significant overrepresentation of positive family history (P = 0.000049), impaired recent memory (P = 0.0123) was observed among p.Leu444Pro carriers. Further, subgroup analysis for PD, PD-MCI and PDD, revealed statistically significant higher frequency of early age at onset (P = 0.0455), positive family history (P = 0.0025), higher UPDRS III score (off state) (P = 0.006), advanced H&Y stage (P = 0.045) and anxious behaviour (P = 0.0124) among p.Leu444Pro positive patients. CONCLUSION: The p.Leu444Pro mutation of GBA was found in patients with PD, PDD, DLB, PSP and AD. An Overall higher frequency of positive family history and impaired recent memory are significantly associated with for p.Leu444Pro carriers from eastern India. Our study also ascertains contribution of p.Leu444Pro to an earlier onset of PD, PD-MCI and PDD, higher UPDRS III score (off state) against positive family history background. Furthermore, taking into consideration other Indian studies, we can conclude that p.Leu444Pro mutation plays a limited role in PD and other neurodegenerative disorders.
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Demência/genética , Glucosilceramidase/genética , Mutação de Sentido Incorreto , Transtornos Parkinsonianos/genética , Adulto , Idoso , Feminino , Frequência do Gene , Humanos , Índia , Masculino , Pessoa de Meia-IdadeRESUMO
CONTEXT: Studies from the different ethnic regions of the world have reported variable results on association of APOE gene polymorphism in stroke. AIM: The aim of this study is to find out the possible association of APOE polymorphism in stroke patients in ethnic Bengali population. SETTINGS AND DESIGN: A prospective case-control study was undertaken in the Department of Neurology, Burdwan Medical College, Burdwan, West Bengal, India, over a period of 3 years. METHODS: We collected 10 ml venous blood samples from 148 clinically and radiologically diagnosed acute stroke patients (80 of ischemic stroke and 68 of intracerebral hemorrhage) and consecutive 108 ethnic age- and sex-matched controls, in ethylenediaminetetraacetic acid vials after informed written consent. Genomic DNA was prepared at S.N. Pradhan Centre of Neurosciences, University of Calcutta, Kolkata, India. Exotic single-nucleotide polymorphisms (rs429358, rs 7412) were analyzed by polymerase chain reaction-restriction fragment length polymorphism for genotype of APOE. RESULTS: The frequencies of different APOE allele among 80 ischemic stroke patients were 5.6% (n = 9) for E2, 75.68% (n = 121) for E3, and 18.7% (n = 30) for E4. The E3 allele is significantly over-represented (P = 0.004) in controls compared to the patients (88% in controls vs 75.6% ischemic stroke patients and 80% hemorrhagic patients). A significantly high frequency of APOE4 allele was observed in ischemic (18.7%) and hemorrhagic patients (11%) compared to controls (8%). The E4 allele plays a major risk for developing ischemic stroke [odds ratio (OR) = 2.744; 95% confidence interval (CI): 1.43-5.10] and E3 plays a protective role for hemorrhagic stroke (OR = 0.53; 95% CI: 0.29-0.96), while E4 allele plays a nonsignificant (P = 0.31) increase in trend in hemorrhage stroke (OR = 1.4). CONCLUSIONS: There is significant association of APOE gene polymorphism in stroke patients of ethnic Bengali population. The E4 allele increases significant risk for development of ischemic strokes, and it also plays nonsignificant increase in trend in hemorrhagic strokes.