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1.
Front Cardiovasc Med ; 10: 1223954, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38099220

RESUMO

Assessing regional wall motion abnormalities (RWMA) in the myocardium may provide early diagnosis and treat chronic remodeling in STEMI patients. We assessed RWMA in 217 subjects with anterior STEMI admitted to Era University Hospital in Lucknow, UP, India. Besides abnormalities in the LAD territory, sub-sets of patients exhibited diffuse regional myocardial dysfunction. Interestingly, variations in serum electrolytes, specifically sodium and potassium, significantly affected the distribution and frequency of RWMA. Notably, RWMA occurred in the basal septum, apical septum, apex, and lateral wall in the anterior STEMI group. Additionally, the rate of regional dysfunction varied with serum urea and creatinine levels. This suggests that anterior STEMI can manifest myocardial abnormalities beyond the LAD territory. These findings indicate that ST-segment elevation might not be specific, possibly influenced by electrolyte changes affecting cardiac rhythm. Therefore, diagnosing and correcting region-specific wall motion abnormalities and electrolyte imbalances may improve outcomes in STEMI patients.

2.
Wiad Lek ; 76(6): 1378-1384, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37463371

RESUMO

OBJECTIVE: The aim: To study the clinical and the genetic association of 5-HTTVNTR and the 5-HTTLPR polymorphisms in women with FMS. PATIENTS AND METHODS: Materials and methods: 105 FMS patients and 105 controls were enrolled in the study. Polymerase chain method was used to analyse the 5-HTTLPR & 5-HTTVNTR gene polymorphism. The psychopathology status of the 105 FMS patients and 105 healthy controls was assessed using the Beck Depression Inventory (BDI) and the Symptom Checklist-90-Revised (SCL-90-R) questionnaires. RESULTS: Results: In FMS patients and controls, the 10/10, 10/12, and 12/12 genotypes of the 5-HTTVNTR polymorphism were found in 3.8% and 2.9%, 20% and 15.2%, and 76.28% and 81.90%, respectively. Additionally, the L/L, S/L, and S/S genotypes of the 5-HTTLPR polymorphism were found in 4.8% and 2.9%, 36.2% and 40%, 59% and 57.1%, in FMS patients and healthy controls, respectively. There were no significant differences in the frequency of genotypes between FMS patients and controls. There were no significant differences in the BDI and the SCL-90-R scores according to the serotonin transporter genotypes. CONCLUSION: Conclusions: We found no significant difference between 5-HTT gene polymorphism (5-HTTVNTR and 5-HTTLPR) and the psychiatric test results (P>0.05) in FMS patients. Hence, we conclude that serotonin gene polymorphism (5-HTTLPR & 5-HTTVNTR) is not associated with FMS in north Indian women. Our results suggests that the serotonin transporter polymorphism does not seem to be a susceptibility factor for FMS.


Assuntos
Fibromialgia , Proteínas da Membrana Plasmática de Transporte de Serotonina , Humanos , Feminino , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Fibromialgia/genética , Polimorfismo Genético , Genótipo
3.
Mol Genet Genomics ; 298(4): 803-812, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37149837

RESUMO

Diabetes is known to increase susceptibility to hypertension due to increase in inflammation, oxidative stress, and endothelial dysfunction, leading to vascular stiffness. The polytherapy might lead to several drug-drug interactions (DDIs), which cause certain life-threatening complications such as diabetic nephropathy and hypoglycaemia. So, in this review we focused on drug-drug interactions and impact of genetic factors on drug responses for better disease management. Drug-drug interactions (DDIs) may act either synergistically or antagonistically. For instance, a combination of metformin with angiotensin II receptor antagonist or angiotensin-converting enzyme inhibitors (ACEIs) synergistically improves glucose absorption, whereas the same hypertensive drug combination with sulphonylurea might cause severe hypoglycaemia sometimes. Thiazolidinediones (TDZs) can cause fluid retention and heart failure when taken alone, but a combination of angiotensin II receptor antagonist with TZDs prevents these side effects. Interindividual genetic variation affects the DDI response. We found two prominent genes, GLUT4 and PPAR-γ, which are common targets for most of the drug. So, all of these findings established a connection between drug-drug interaction and genetics, which might be used for effective disease management.


Assuntos
Diabetes Mellitus , Hipertensão , Hipoglicemia , Humanos , Farmacogenética , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/genética , Hipertensão/tratamento farmacológico , Hipertensão/genética , Antagonistas de Receptores de Angiotensina/efeitos adversos
4.
Aging Dis ; 14(2): 299-308, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37008057

RESUMO

COVID-19 has been associated with various hyper-inflammatory conditions (HICs) such as macrophage activation, hematological dysfunction, cytokinaemia, coagulopathy, and liver inflammation. However, it is not clear if the differences in the disease severity and mortality shown by male and female COVID-19 patients are associated with these HICs. Here, we review the literature and present supporting laboratory data on the gender differences associated with various HICs in COVID-19 patients. We measured plasma/serum levels of various HIC specific clinical markers in severe male (N=132) and severe female (N=78) COVID-19 patients. The result revealed that all clinical markers were highly elevated above the normal in both male and female COVID-19 patients. However, a comparison of AUROC (area under the receiving operative characteristics) of specific clinical markers revealed that elevation in serum ferritin (marker for macrophage activation), and neutrophil to lymphocyte (N/L) ration (marker for hematological dysfunction) was much higher in male compared to the female COVD-19 patients. Further, univariate regression analyses revealed that male COVID-19 patients had two times higher risks than female patients for developing macrophage activation (OR 2.36, P=0.004)), hematological dysfunctions (OR 2.23, P=0.01), coagulopathy (OR 2.10, P=0.01), and cytokinaemia (OR 2.31, P=0.01). Similar results were obtained in bivariate analyses. Survival curve analysis showed that male COVID-19 patients had relatively short survival duration than female COVID-19 patients (hazard ratio 2.0, 95% CI 1.3-3.7, P=0.01). The above findings suggest that the high mortality rate in male COVID-19 patients compared to the female could be due to higher prevalence and severity of various HICs.

5.
Indian J Clin Biochem ; 38(3): 287-296, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36407685

RESUMO

The new competency-based medical education undergraduate curriculum (CBMC) was launched for the 2019 admission batch of MBBS students. The programme is designed to create an "Indian Medical Graduate" (IMG) possessing the requisite knowledge, skills, attitudes, values and responsiveness, so that the graduate may function appropriately and effectively as a physician of first contact with the community while being globally relevant. Given that implementation of this curriculum is still in its infancy across the country, we stand to gain from a unified approach to its implementation. Phase I of the curriculum includes anatomy, physiology, and biochemistry along with professional and personal development modules. Biochemistry enjoys an enviable position in the medical curriculum as it explains the molecular basis of diseases. We present an appraisal of the curriculum in Biochemistry by reviewing the components against Harden's six themes which are considered when planning or developing a curriculum. Further, five core components of CBME are selected on the basis of three research papers to characterize underlying assumptions of CBME to suggest ways of logical implementation for achieving the competencies expected of the Indian Medical Graduate. The insight gained shall help students to be equipped with competencies which they shall be able to use in their day- to- day work, which shall ultimately help benefit patient care and the society at large. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01088-y.

6.
Int J Immunogenet ; 50(1): 5-11, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36323530

RESUMO

Coronavirus disease-2019 (COVID-19) is pro-inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin-6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID-19 patients. The differential expression of IL6 cytokine in COVID-19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (-597G > A and -174G > C) with the severity of COVID-19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID-19. Genotyping of two selected SNPs, rs1800795 (-174G > C) and rs1800797 (-597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In our study, individuals with GC genotypes of IL6 (-174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID-19 severity with rs1800797 (-597G > A) polymorphism. The COVID-19 severity was significantly higher in individuals having 'C' allele of IL6 (-174G > C) polymorphism (p = .014). Linkage disequilibrium between rs1800795 (-174G > C) and rs1800797 (-597G > A) showed that individuals having AC* haplotype significantly association with COVID-19 severity (p = .034). Our results suggest that 'C' allele of rs1800795 (-174G > C) polymorphism of IL6 may be the risk allele for severity of COVID-19 in North Indian population.


Assuntos
COVID-19 , Interleucina-6 , Humanos , Interleucina-6/genética , Predisposição Genética para Doença , COVID-19/genética , Genótipo , Polimorfismo de Nucleotídeo Único , Frequência do Gene
7.
Wiad Lek ; 75(10): 2439-2444, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36472276

RESUMO

OBJECTIVE: The aim: To determine the clinical and the genetic association of the COMT rs4680 SNP in women with FMS. PATIENTS AND METHODS: Materials and methods: Extracted DNA from peripheral blood samples were utilized as template for the PCR and RFLP analysis. RESULTS: Results: A significant difference was found in the distribution of the COMT genotype between FMS patients and controls (P<0.05). The frequency of GG, AG, AA genotypes were 12%, 72%, 21% in FMS patients and 32%, 62%, 11% in controls. The clinical features of FMS reveal that FIQR and the severity of pain measured by VAS were significantly associated with the COMT rs4680 SNP (P=0.042; P=0.016). The co-dominant model for GG verse v. AG genotype (P=0.004) and AG v. AA genotype (P=0.002) has shown to be high risk for FMS. An increased risk of FMS in the dominant model for (AG+AA) v. GG genotype (P=0.001) and no significant difference was found between (GG+AG) v. AA genotype (P=0.08) in the recessive model. The result indicated that A allele considerably increase the risk of FMS (P=0.004) in comparison to the G allele. CONCLUSION: Conclusions: AA genotype and A allele of the COMT rs4680 SNP were significantly associated with severity in FMS patients and also plays a significant role in the clinical manifestation of this disease.


Assuntos
Catecol O-Metiltransferase , Fibromialgia , Humanos , Feminino , Catecol O-Metiltransferase/genética , Fibromialgia/genética , Polimorfismo Genético , Genótipo , Polimorfismo de Nucleotídeo Único
8.
Indian J Otolaryngol Head Neck Surg ; 74(2): 225-233, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35813773

RESUMO

The Interprofesional collaborative practice (IPCP) is the need of the hour for improved patient care. The procedure of tracheotomy is a life saving procedure and the implementation of the Interprofessional collaborative practice module for the same comprising of the ENT surgeon, Physiotherapist, Nursing staff, OT and Trauma technician decreases the number of complications. This study was carried out to develop and evaluate the Interprofessional collaborative practice module for Tracheostomy. The project has been carried out as a prospective before and after study with the departments of ENT, nursing and Allied health sciences. The facilitators were from the above departments.They were sensitized and developed the Interprofessional education (IPE team),which then collaborated to develop the IPCP module.This IPE team after faculty meetings developed the module with learning objectives, teaching learning methods and methods of assessment. Standardized Readiness scale for Interprofessional Learning Scale (RIPLS), was adopted for the module. The questionnaires for assessment and the module were structured and validated.The template of reflection was compiled for the execution of the module. The students training comprised of the demonstration session, baseline Team OSCE, practice sessions and the final Team OSCE. The baseline and final Team OSCE scores,reflections and RIPLS scores were compared. Team OSCE scores baseline vs Final for IPCP competencies i.e. Competency 1-Values and Ethics for Interprofessional Practice, Competency 2-Roles and Responsibilities, Competency 3-Interprofessional Communication, Competency 4-Teams and Teamwork during Pretracheostomy (PreT),Tracheostomy(T) and PostTracheostomy (PostT) were calculated. Faculty observations: TOSCE scores (pre T/T/postT) significantly improved for all the four IPCP competencies (p < 0.001). Self evaluation did not get any significant improvements in PreT and T but significant improvement (P < 0.001) in competency 2 for Post T. Peer evaluation there was significant improvement for the competencies 1 & 2 and overall as well (p < 0.001) during preT, competency 2 during T and competency 2, 3, 4 during PostT. The reflections had a highly significant change from baseline to final (p < 0.001).On final evaluation for the Readiness scale for Interprofessional learning the faculties and students had significant changes in opinions in all the items of the readiness scale (p < 0.05). The project was able to achieve a motivated IPE team which could successfully structure and effectively conduct the IPCP module for the procedure of tracheostomy.

9.
J Food Biochem ; 46(10): e14262, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35796388

RESUMO

SARS-CoV-2 has been responsible for causing 6,218,308 deaths globally till date and has garnered worldwide attention. The lack of effective preventive and therapeutic drugs against SARS-CoV-2 has further worsened the scenario and has bolstered research in the area. The N-terminal and C-terminal RNA binding domains (NTD and CTD) of SARS-CoV-2 nucleocapsid protein represent attractive therapeutic drug targets. Naturally occurring compounds are an excellent source of novel drug candidates due to their structural diversity and safety. Ten major bioactive compounds were identified in ethanolic extract (s) of Cinnamomum zeylanicum, Cinnamomum tamala, Origanum vulgare, and Petroselinum crispum using HPLC and their cytotoxic potential was determined against cancer and normal cell lines by MTT assay to ascertain their biological activity in vitro. To evaluate their antiviral potential, the binding efficacy to NTD and CTD of SARS-CoV-2 nucleocapsid protein was determined using in silico biology tools. In silico assessment of the phytocomponents revealed that most of the phytoconstituents displayed a druglike character with no predicted toxicity. Binding affinities were in the order apigenin > catechin > apiin toward SARS-CoV-2 nucleocapsid NTD. Toward nucleocapsid CTD, the affinity decreased as apigenin > cinnamic acid > catechin. Remdesivir displayed lesser affinity with NTD and CTD of SARS-CoV-2 nucleocapsid proteins than any of the studied phytoconstituents. Molecular dynamics (MD) simulation results revealed that throughout the 100 ns simulation, SARS-CoV-2 nucleocapsid protein NTD-apigenin complex displayed greater stability than SARS-CoV-2 nucleocapsid protein NTD-cinnamic acid complex. Hence, apigenin, catechin, apiin and cinnamic acid might prove as effective prophylactic and therapeutic candidates against SARS-CoV-2, if examined further in vitro and in vivo. PRACTICAL APPLICATIONS: Ten major bioactive compounds were identified in the extract(s) of four medicinally important plants viz. Cinnamomum zeylanicum, Cinnamomum tamala, Origanum vulgare and Petroselinum crispum using HPLC and their biological activity was also evaluated against cancer and normal cell lines. Interestingly, while all extract(s) wielded significant cytotoxicity against cancer cells, no significant toxicity was found against normal cells. The outcome of the results prompted evaluation of the antiviral potential of the ten bioactive compounds using in silico biology tools. The present study emphasizes on the application of computational approaches to understand the binding interaction and efficacy of the ten bioactive compounds from the above plants with SARS-CoV-2 nucleocapsid protein N-terminal and C-terminal RNA binding domains in preventing and/or treating COVID-19 using in silico tools. Druglikeness and toxicity profiles of the compounds were carried out to check the therapeutic application of the components. Additionally, molecular dynamics (MD) simulation was performed to check the stability of ligand-protein complexes. The results provided useful insights into the structural binding interaction(s) that can be exploited for the further development of potential antiviral agents targeting SARS-CoV-2 especially since no specific therapy is still available to combat the rapidly evolving virus and the existing treatment is more or less symptomatic which makes search for novel antiviral agents all the more necessary and crucial.


Assuntos
Tratamento Farmacológico da COVID-19 , Catequina , Laurus , Origanum , Antivirais/química , Antivirais/farmacologia , Apigenina , Cinamatos , Cinnamomum zeylanicum/metabolismo , Suplementos Nutricionais , Laurus/metabolismo , Ligantes , Petroselinum/metabolismo , SARS-CoV-2
10.
Glob Med Genet ; 9(2): 90-96, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35707778

RESUMO

Tuberculosis (TB) continues to be a major infectious disease affecting individuals worldwide. Current TB treatment strategy recommends the standard short-course chemotherapy regimen containing first-line drug, i.e., isoniazid, rifampicin, pyrazinamide, and ethambutol to treat patients suffering from drug-susceptible TB. Although Mycobacterium tuberculosis , the causing agent, is susceptible to drugs, some patients do not respond to the treatment or treatment may result in serious adverse reactions. Many studies revealed that anti-TB drug-related toxicity is associated with genetic variations, and these variations may also influence attaining maximum drug concentration. Thus, inter-individual diversities play a characteristic role by influencing the genes involved in drug metabolism pathways. The development of pharmacogenomics could bring a revolution in the field of treatment, and the understanding of germline variants may give rise to optimized targeted treatments and refine the response to standard therapy. In this review, we briefly introduced the field of pharmacogenomics with the evolution in genetics and discussed the pharmacogenetic impact of genetic variations on genes involved in the activities, such as anti-TB drug transportation, metabolism, and gene regulation.

11.
Glob Med Genet ; 9(2): 63-71, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35707783

RESUMO

Diabetes has become a pandemic as the number of diabetic people continues to rise globally. Being a heterogeneous disease, it has different manifestations and associated complications in different individuals like diabetic nephropathy, neuropathy, retinopathy, and others. With the advent of science and technology, this era desperately requires increasing the pace of embracing precision medicine and tailoring of drug treatment based on the genetic composition of individuals. It has been previously established that response to antidiabetic drugs, like biguanides, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and others, depending on variations in their transporter genes, metabolizing genes, genes involved in their action, etc . Responsiveness of these drugs also relies on epigenetic factors, including histone modifications, miRNAs, and DNA methylation, as well as environmental factors and the lifestyle of an individual. For precision medicine to make its way into clinical procedures and come into execution, all these factors must be reckoned with. This review provides an insight into several factors oscillating around the idea of precision medicine in type-2 diabetes mellitus.

12.
Indian J Clin Biochem ; 37(1): 69-76, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35125695

RESUMO

Dopamine transporter takes released dopamine back into presynaptic terminals and has been implicated in several aging disorders including depression. The present study was designed to demonstrate dopamine gene polymorphism, its circulatory levels, biochemical and oxidative stress parameters in geriatric population with and without depression. Thirty geriatric patients with depression and thirty age and sex matched normal controls were genotyped for Dopamine Active Transporter (DAT TaqA1 and DAT VNTR) gene polymorphisms using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism method. The frequency of genotypes and alleles were compared in study groups. Biochemical markers, oxidative stress parameters, and dopamine levels were also measured using standard protocols and compared between patients and controls. The frequency distribution of DAT TaqA1 and DAT VNTR genotypes and alleles in patients were not statistically significant as compared to controls. At DAT TaqA1 gene polymorphism we found that the levels of dopamine were significantly high in genotypes A1A2 as compared to A2A2 (p ≤ 0.01). The present study demonstrated elevated levels of Catalase, Lipid Peroxide, and Glutathione Reductase, whereas decreased levels of Superoxide Dismutase, Dehydroepiandrosterone, Glutathione Peroxidase and Melatonin, in depressive patients as compared to controls. Our results clearly suggested that elevated mean levels of Catalase, Lipid Peroxides and Glutathione Reductase and decreased levels of Dehydroepiandrosterone, Superoxide Dismutase, Glutathione Peroxidase and Melatonin in depressed individuals may be a consequence of depression. Moreover, DAT TaqA1 allele A1 has a protective effect with high dopamine levels and DAT VNTR genotype 10R/10R has the highest protective effect followed by 9R/10R and 10R/11R.

13.
Egypt J Med Hum Genet ; 23(1): 145, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37521849

RESUMO

Background: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic which has emerged as a new challenge for the medical sciences. Severity of COVID-19 is mostly determined with overexpressed proinflammatory cytokines eventually leading to endothelial dysfunction causing vital organ injury, especially in the lungs. It has been postulated that various genetic mutations might be associated with an increased risk of disease severity in COVID-19. This study was thus carried out to determine the association of rs1800896 and rs1800872 genetic polymorphism in IL-10 gene in determining COVID-19 severity. Methods: The study included 160 RT-PCR confirmed COVID-19 patients with mild (n = 85) and severe (n = 75) conditions. All subjects were genotyped for Interleukin-10 (rs1800896 and rs1800872) gene polymorphisms using PCR-RFLP technique followed by statistical analysis. Results: This study found a significant gender and age-based discrepancy in COVID-19 severity with 1.85-and 3.81-fold increased risk of COVID-19 in males of mild and severe groups as compared to females (p = 0.046 and p < 0.001) and 4.35-fold high risk in subjects ≥ 50 (p < 0.001). Genotyping analysis showed that IL-10 (rs1800872) gene polymorphism was strongly associated with COVID-19 severity (p = 0.01) whereas, IL-10 rs1800896 polymorphism was not found to confer the risk of COVID-19 severity in our population. Conclusion: In this regard, the present study provided an evidence that IL-10 (rs1800872) gene polymorphism is strongly associated with COVID-19 severity and CC genotype confer a protective role in preventing severe disease progression. More detailed studies with a larger sample size on the genetic variations are required to establish the role of studied IL-10 gene polymorphisms with COVID-19 severity.

14.
J Gynecol Obstet Hum Reprod ; 50(9): 102159, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33965650

RESUMO

Human papillomaviruses (HPV) infection is a major causative agent and strongly associated with the development of cervical cancer. Understanding the mechanisms of HPV-induced cervical cancer is extremely useful in therapeutic strategies for primary prevention (HPV vaccines) and secondary prevention (screening and diagnosis of precancerous lesions). However, due to the lack of proper implementation of screening programs in developing countries, cervical cancer is usually diagnosed at advanced stages that result in poor treatment responses. Nearly half of the patients will experience disease recurrence within two years post treatment. Therefore, it is vital to identify new tools for early diagnosis, prognosis, and treatment prediction. MicroRNAs (miRNAs) are small non-coding RNAs, implicated in posttranscriptional regulation of gene expression. Growing evidence has shown that abnormal miRNA expression is associated with cervical cancer progression, metastasis, and influences treatment outcomes. In this review, we provide comprehensive information about miRNA and their potential utility in cervical cancer diagnosis, prognosis, and clinical management to improve patient outcomes.


Assuntos
MicroRNAs/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/etiologia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , MicroRNAs/administração & dosagem , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/tratamento farmacológico , Prognóstico
15.
J Med Virol ; 93(9): 5446-5451, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33990973

RESUMO

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a global health issue and develops into a broad range of illnesses from asymptomatic to fatal respiratory diseases. SARS-CoV-2 infection is associated with oxidative stress that triggers cytokine production, inflammation, and other pathophysiological processes. Glutathione-S-transferase (GST) is an important enzyme that catalyzes the conjugation of glutathione (GSH) with electrophiles to protect the cell from oxidative damage and participates in the antioxidant defense mechanism in the lungs. Thus, in this study, we investigated the role of GSTM1 and GSTT1 gene polymorphism with COVID-19 susceptibility, as well as its outcome. The study included 269 RT-PCR confirmed COVID-19 patients with mild (n = 149) and severe (n = 120) conditions. All subjects were genotyped for GSTM1 and GSTT1 by multiplex polymerase chain reaction (mPCR) followed by statistical analysis. The frequency of GSTM1-/- , GSTT1-/- and GSTM1-/- /GSTT1-/- was higher in severe COVID-19 patients as compared to mild patients but we did not observe a significant association. In the Cox hazard model, death was significantly 2.28-fold higher in patients with the GSTT1-/- genotype (p = 0.047). In combination, patients having GSTM1+/+ and GSTT1-/- genotypes showed a poor survival rate (p = 0.02). Our results suggested that COVID-19 patients with the GSTT1-/- genotype showed higher mortality.


Assuntos
COVID-19/genética , Predisposição Genética para Doença , Glutationa Transferase/genética , Polimorfismo Genético , SARS-CoV-2/patogenicidade , Adulto , Idoso , Alelos , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19 , Feminino , Seguimentos , Expressão Gênica , Frequência do Gene , Glutationa/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Modelos de Riscos Proporcionais , Índice de Gravidade de Doença
16.
Infect Genet Evol ; 91: 104801, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33676010

RESUMO

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has first emerged from China in December 2019 and causes coronavirus induced disease 19 (COVID-19). Since then researchers worldwide have been struggling to detect the possible pathogenesis of this disease. COVID-19 showed a wide range of clinical behavior from asymptomatic to severe acute respiratory disease syndrome. However, the etiology of susceptibility to severe lung injury is not yet fully understood. Angiotensin-converting enzyme1 (ACE1) convert angiotensin I into Angiotensin II that was further metabolized by ACE 2 (ACE2). The binding ACE2 receptor to SARS-CoV-2 facilitate its enter into the host cell. The interaction and imbalance between ACE1 and ACE2 play a crucial role in the pathogenesis of lung injury. Thus, the aim of this study was to investigate the association of ACE1 I/D polymorphism with severity of Covid-19. The study included RT-PCR confirmed 269 cases of Covid-19. All cases were genotyped for ACE1 I/D polymorphism using polymerase chain reaction and followed by statistical analysis (SPSS, version 15.0). We found that ACE1 DD genotype, frequency of D allele, older age (≥46 years), unmarried status, and presence of diabetes and hypertension were significantly higher in severe COVID-19 patient. ACE1 ID genotype was significantly independently associated with high socio-economic COVID-19 patients (OR: 2.48, 95% CI: 1.331-4.609). These data suggest that the ACE1 genotype may impact the incidence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.


Assuntos
Substituição de Aminoácidos , COVID-19/epidemiologia , COVID-19/genética , Predisposição Genética para Doença , Peptidil Dipeptidase A/genética , Polimorfismo Genético , SARS-CoV-2/patogenicidade , Adulto , Fatores Etários , Idoso , Alelos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Ácido Aspártico/genética , Ácido Aspártico/metabolismo , Doenças Assintomáticas , COVID-19/mortalidade , COVID-19/virologia , Comorbidade , Diabetes Mellitus , Feminino , Regulação da Expressão Gênica , Frequência do Gene , Interações Hospedeiro-Patógeno/genética , Humanos , Hipertensão , Índia/epidemiologia , Isoleucina/genética , Isoleucina/metabolismo , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/metabolismo , Fatores de Risco , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Análise de Sobrevida
17.
Afr Health Sci ; 21(3): 1163-1171, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35222579

RESUMO

BACKGROUND: Endothelial nitric oxide synthase (eNOS) and potassium voltage-gated channel subfamily J member 11 (KCNJ11) could be the candidate genes for coronary artery disease (CAD). This study investigated the relationship of the eNOS (rs1799983) and KCNJ11 (rs5219) polymorphisms with the presence and severity of CAD in the North Indian population. METHODS: This study included 300 subjects, 150 CAD cases and 150 healthy controls. Single nucleotide polymorphism was evaluated by Polymerase chain reaction and Restriction fragment length polymorphism (PCR-RFLP). Analysis was performed by SPSS (version 21.0). RESULTS: We observed that KK genotype of KCNJ11E23K (rs5219) polymorphism (P=0.0001) genotypes and K allele (P=0.0001) was found to be a positive risk factor and strongly associated with CAD. In the case of eNOSG894T (rs1799983) there was no association found with CAD. CONCLUSION: These results illustrate the probability of associations between SNPs and CAD although specific genetic polymorphisms affecting ion channel function and expression have still to be clarified by further investigations involving larger cohorts.


Assuntos
Doença da Artéria Coronariana , Óxido Nítrico Sintase Tipo III , Povo Asiático , Estudos de Casos e Controles , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Predisposição Genética para Doença , Genótipo , Humanos , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Fatores de Risco
18.
MedEdPublish (2016) ; 9: 248, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-38058941

RESUMO

This article was migrated. The article was marked as recommended. The unprecedented lockdown caused by the COVID-19 pandemic has resulted in an academic frenzy for students and teachers alike. Medical schools have had to take charge of the situation. Distance learning has become the norm. At the same time, online assessment is being considered to be rolled out to facilitate learning. Students went home during the lockdown and online classes were conducted for them to avoid any compromise to their learning. Facilitators were concerned about the students' wellbeing as lack of personal contact made it difficult to assess their wellness. The virtual platform can be used as a tool to check the overall health status of the students. Well- being can be discussed in terms of physical, temperamental, cognitive and spiritual health along with their awareness towards the environment, social and professional attitudes. The help of a mentorship program can be sought to get in touch with students. Meetings can be set up with the mentees to help ease out the stress and worry from the student's lives. This article attempts to suggest ways in which the students' contentment can be met with in these trying times. The unprecedented lockdown caused by the COVID-19 pandemic has resulted in an academic frenzy for students and teachers alike. Medical schools have had to take charge of the situation. Distance learning has become the norm. At the same time, online assessment is being considered to be rolled out to facilitate learning. Students went home during the lockdown and online classes were conducted for them to avoid any compromise to their learning. Facilitators were concerned about the students' wellbeing as lack of personal contact made it difficult to assess their wellness. The virtual platform can be used as a tool to check the overall health status of the students. Well- being can be discussed in terms of physical, temperamental, cognitive and spiritual health along with their awareness towards the environment, social and professional attitudes. The help of a mentorship program can be sought to get in touch with students. Meetings can be set up with the mentees to help ease out the stress and worry from the student's lives. This article attempts to suggest ways in which the students' contentment can be met with in these trying times.

20.
Mol Biol Rep ; 46(5): 5433-5441, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31377977

RESUMO

Genetic factors in combination with environmental factors play a critical role in the development type 2 diabetes mellitus (T2DM) which is growing as an epidemic globally. In present study we aim to assess the association of eNOS (G894T, rs1799983) and NET (G1287A, rs5569) genes polymorphism with T2DM. A case-control study including a total of 400 North Indian subjects (200 T2DM cases and 200 controls) was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach to analyze genetic polymorphism. Alleles/genotype frequencies between cases and controls were compared using χ2 and Student's t-tests. Odds ratios and 95% confidence intervals were calculated by logistic regression to assess the relative association between disease and genotypes. In case of NET gene, GG (P = 0.002 in T2DM males, 0.053 in overall T2DM cases) genotype and G allele (P = 0.003 in T2DM males, 0.027 in overall T2DM cases) were found to be a positive risk factors and AG genotype (P = 0.012 in T2DM males) and A allele (P = 0.003 in T2DM males, P = 0.027 in overall T2DM cases) as negative risk factor for T2DM. No association of eNOS gene polymorphism was found with T2DM (P values of all genotypes and alleles were greater than 0.05). NET gene polymorphism might be associated with the risk of T2DM whereas; eNOS gene polymorphism do not confer any risk of T2DM in North Indian Ethnic group. It is hoped that understanding genetic causes of T2DM will lead to earlier diagnosis, preventive measures and more effective and specific treatment.


Assuntos
Diabetes Mellitus Tipo 2/genética , Óxido Nítrico Sintase Tipo III/genética , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/genética , Adulto , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/metabolismo , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Fatores de Risco
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