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1.
Int J Mol Sci ; 22(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205175

RESUMO

The FcγRIIA/CD32A is mainly expressed on platelets, myeloid and several endothelial cells. Its affinity is considered insufficient for allowing significant binding of monomeric IgG, while its H131R polymorphism (histidine > arginine at position 131) influences affinity for multimeric IgG2. Platelet FcγRIIA has been reported to contribute to IgG-containing immune-complexe clearance. Given our finding that platelet FcγRIIA actually binds monomeric IgG, we investigated the role of platelets and FcγRIIA in IgG antibody elimination. We used pharmacokinetics analysis of infliximab (IgG1) in individuals with controlled Crohn's disease. The influence of platelet count and FcγRIIA polymorphism was quantified by multivariate linear modelling. The infliximab half-life increased with R allele number (13.2, 14.4 and 15.6 days for HH, HR and RR patients, respectively). It decreased with increasing platelet count in R carriers: from ≈20 days (RR) and ≈17 days (HR) at 150 × 109/L, respectively, to ≈13 days (both HR and RR) at 350 × 109/L. Moreover, a flow cytometry assay showed that infliximab and monomeric IgG1 bound efficiently to platelet FcγRIIA H and R allotypes, whereas panitumumab and IgG2 bound poorly to the latter. We propose that infliximab (and presumably any IgG1 antibody) elimination is partly due to an unappreciated mechanism dependent on binding to platelet FcγRIIA, which is probably tuned by its affinity for IgG2.


Assuntos
Doença de Crohn/tratamento farmacológico , Imunoglobulina G/genética , Infliximab/administração & dosagem , Receptores de IgG/genética , Adulto , Complexo Antígeno-Anticorpo/genética , Complexo Antígeno-Anticorpo/imunologia , Plaquetas/efeitos dos fármacos , Plaquetas/imunologia , Doença de Crohn/sangue , Doença de Crohn/genética , Doença de Crohn/imunologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Feminino , Citometria de Fluxo , Humanos , Imunoglobulina G/imunologia , Infliximab/farmacocinética , Masculino , Ativação Plaquetária/efeitos dos fármacos , Contagem de Plaquetas , Polimorfismo Genético/genética
2.
BMC Res Notes ; 14(1): 244, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193266

RESUMO

OBJECTIVE: Glutathione S-transferases have been associated with experimental resistance to some drugs. The present study investigated the factors associated with blood pressure control in patients with essential hypertension, especially the role of GSTT1 and GSTM1 genes polymorphisms. This cross-sectional study in Burkina Faso consisted of 200 patients with essential hypertension and under treatment. RESULTS: In the present study, 57.5% (115/200) of patients had their hypertension under control. No statistically significant difference was found between controlled and uncontrolled groups for anthropometric and biochemical parameters as well as for GSTT1 or GSTM1 gene polymorphisms (all p > 0.05). Current alcohol consumption (OR = 3.04; CI 1.88-6.13; p < 0.001), Physical inactivity (OR = 3.07; CI 1.71-5.49; p < 0.001), severe hypertension before any treatment (Grade III [OR = 3.79; CI 2.00-7.17; p < 0.001]) and heart damage (OR = 3, 14; CI 1.59-6.02; p < 0.001) were statistically more frequent in uncontrolled essential hypertensive patients than controlled hypertensive patients.


Assuntos
Predisposição Genética para Doença , Hipertensão , Pressão Sanguínea , Burkina Faso , Estudos de Casos e Controles , Estudos Transversais , Genótipo , Glutationa Transferase/genética , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/genética , Polimorfismo Genético
3.
Biomolecules ; 11(6)2021 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204735

RESUMO

The receptor for advanced glycation-end products (RAGE) is a multiligand receptor with a role in inflammatory and pulmonary pathologies. Hyperactivation of RAGE by its ligands has been reported to sustain inflammation and oxidative stress in common comorbidities of severe COVID-19. RAGE is essential to the deleterious effects of the renin-angiotensin system (RAS), which participates in infection and multiorgan injury in COVID-19 patients. Thus, RAGE might be a major player in severe COVID-19, and appears to be a useful therapeutic molecular target in infections by SARS-CoV-2. The role of RAGE gene polymorphisms in predisposing patients to severe COVID-19 is discussed. .


Assuntos
COVID-19/metabolismo , Inflamação/metabolismo , Estresse Oxidativo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Sistema Renina-Angiotensina , Animais , COVID-19/genética , COVID-19/patologia , Humanos , Inflamação/genética , Inflamação/patologia , Polimorfismo Genético , Receptor para Produtos Finais de Glicação Avançada/genética , Fatores de Risco , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença
4.
Anticancer Res ; 41(7): 3247-3252, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230118

RESUMO

Cancer immunotherapy is an evolving field of research. Cytokines have been conceptualized as an anticancer therapy for longer than most other cancer immunotherapy modalities. Yet, to date, only two cytokines are FDA-approved: IFN-α and IL-2. Despite the initial breakthrough, both agents have been superseded by other, more efficacious agents such as immune checkpoint inhibitors. Several issues persist with cytokine-based cancer therapies; these are broadly categorised into a) high toxicity and b) low efficacy. Despite the only moderate benefits with early cytokine-based cancer therapies, advances in molecular engineering, genomics, and molecular analysis hold promise to optimise and reinstate cytokine-based therapies in future clinical practice. This review considers five important concepts for the successful clinical application of cytokine-based cancer therapies including: (i) improving pharmacokinetics and pharmacodynamics, (ii) improving local administration strategies, (iii) understanding context-dependent interactions in the tumour-microenvironment, (iv) elucidating the role of genetic polymorphisms, and (v) optimising combination therapies. IL-10 has been the focus of attention in recent years and is discussed herein as an example.


Assuntos
Citocinas/farmacologia , Citocinas/uso terapêutico , Interleucina-10/farmacologia , Interleucina-10/uso terapêutico , Neoplasias/imunologia , Neoplasias/terapia , Animais , Humanos , Imunoterapia/métodos , Polimorfismo Genético/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(7): 681-685, 2021 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-34247378

RESUMO

OBJECTIVE: To assess the association of polymorphisms of receptor of advanced glycation end products (RAGE) gene, monocyte to high-density lipoprotein cholesterol ratio (MHR) and variability of heart rate among patients with coronary heart disease (CHD). METHODS: 120 patients with CHD and 120 healthy individuals were respectively selected as the observation group and the control group. Allelic and genotypic differences of -429T>C, 1704G>T, 82G>S, MHR ratio and heart rate variability between the two groups and patients with different severity were analyzed. The correlation between their genotypes and MHR ratio and heart rate variability was analyzed. RESULTS: The 82G>S polymorphism of the RAGE gene and the allelic difference between the two groups and patients with different severity were statistically significant (P< 0.05). Compared with the control group and patients with mild to moderate phenotype, monocyte, total cholesterol, triglyceride, low density lipoprotein, MHR, low frequency in the observation group and patients with severe symptoms were significantly higher, while their high density lipoprotein, standard deviation of NN intervals (SDNN), standard deviation average of NN intervals (SDANN), root mean square successive differences, percentage of differences exceeding 50ms between adjacent normal number of intervals (PMN50), high frequency (HF) were significantly lower. The gene frequencies of G-Gly-T, T-Gly-T, G-Ser-T and G-Gly-C were correlated with SDNN, SDANN, rMSSD, PMN50, HF and MHR, but negatively correlated with low frequency. CONCLUSION: Polymorphisms of the RAGE gene in patients with coronary heart disease are associated with the MHR ratio and heart rate variability, which can be used as markers for the diagnosis and efficacy evaluation.


Assuntos
Doença das Coronárias , Produtos Finais de Glicação Avançada , Doença das Coronárias/genética , Frequência do Gene , Frequência Cardíaca , Humanos , Polimorfismo Genético
6.
Indian J Dent Res ; 32(1): 69-73, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34269240

RESUMO

Background: An individual's risk towards development of cancer depends not only on environmental factors or extrinsic exposure to carcinogens but also on individual's genetic susceptibility. Aim: To determine two genetically established parameters such as prevalence of GSTM1 null polymorphism and analysis of Palmar dermatoglypics (PD) in patients with Oral Leukoplakia (OL) and Controls. Materials and Methods: Group I (cases) 30 patients with established histopathological diagnosis of OL and Group II (controls) 30 patients without any habits of tobacco, alcohol usage and without OL were selected. After informed consent, the palm prints were recorded using a Canon PIXMA MP250 scanner and 2 ml of blood was collected and transported under cold cycle and taken for evaluation of GSTM1 null polymorphism using Multiplex PCR. Results: There exists a highly significant difference in GSTM1 null polymorphism (p-0.002), Finger ridge patterns (arches- p-0.027, loops p-0.001, whorls p-0.001), hypothenar pattern (p-0.015), ATD angle (p-0.001), AB count (p-0.007) between cases and controls. Similarly, when analysing the GSTM1 null polymorphism with PD among cases, there exists a significant association between loops (p-0.001), AB count (p-0.058) and hypothenar pattern (p-0.076), respectively 43% of OL cases had alteration in both which implies that those patients are at a higher risk of developing cancer. Conclusion: Not all patients who smoke or chew tobacco develop cancer. This could probably be due to the individual's genetic susceptibility. Environment gene interactions, in the form of GSTM1 polymorphism, and carcinogenesis, share links that can help in the prediction of risk for oral cancer development, and use of such markers can aid in prediction of oral cancer susceptibility in exposed individuals. Palm prints once formed do not change throughout life and are not influenced by environment. It can also serve as genetic markers to predict the risk of occurrence of oral cancer.


Assuntos
Glutationa Transferase , Leucoplasia Oral/genética , Neoplasias Bucais , Estudos de Casos e Controles , Predisposição Genética para Doença , Glutationa Transferase/genética , Humanos , Neoplasias Bucais/genética , Polimorfismo Genético , Fatores de Risco , Fumar , Tabaco sem Fumaça
7.
J Int Med Res ; 49(7): 3000605211019263, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34275374

RESUMO

OBJECTIVE: To investigate the relationship between angiotensin (AGT) rs2493132 gene polymorphism and the risk of developing non-alcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD) in the Chinese Han population. METHODS: Polymerase chain reaction was performed to determine AGT genotypes. Anthropometric and clinical data were investigated and statistically analyzed in the clinical laboratory department of Qingdao Municipal Hospital. RESULTS: The AGT rs2493132 CT + TT genotype was an important risk factor for CAD in patients with NAFLD and NAFLD + CAD in healthy controls. The AGT rs2493132 T allele increased the risk of NAFLD + CAD in healthy controls. The AGT rs2493132 CT + TT genotype and T allele also significantly increased the risk of CAD in patients with NAFLD after adjustments for age, sex, and body mass index. In addition, AGT rs2493132 T allele carriers showed higher total cholesterol (TC) and low-density lipoprotein (LDL) levels compared with non-carriers. CONCLUSIONS: The AGT rs2493132 CT + TT genotype and T allele significantly increased the risk of developing CAD in patients with NAFLD in the Chinese Han population. The AGT rs2493132 T allele was associated with increased serum TC and LDL levels.


Assuntos
Doença da Artéria Coronariana , Hepatopatia Gordurosa não Alcoólica , Angiotensinas , Grupo com Ancestrais do Continente Asiático/genética , China , Doença da Artéria Coronariana/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
8.
Int J Mol Sci ; 22(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072457

RESUMO

Cytochrome P450 3A7 (CYP3A7) is a fetal/neonatal liver enzyme that participates in estriol synthesis, clearance of all-trans retinoic acid, and xenobiotic metabolism. Compared to the closely related major drug-metabolizing enzyme in adult liver, CYP3A4, the ligand binding and catalytic capacity of CYP3A7 are substantially reduced. To better understand the structural basis for these functional differences, the 2.15 Å crystal structure of CYP3A7 has been solved. Comparative analysis of CYP3A enzymes shows that decreased structural plasticity rather than the active site microenvironment defines the ligand binding ability of CYP3A7. In particular, a rotameric switch in the gatekeeping amino acid F304 triggers local and long-range rearrangements that transmit to the F-G fragment and alter its interactions with the I-E-D-helical core, resulting in a more rigid structure. Elongation of the ß3-ß4 strands, H-bond linkage in the substrate channel, and steric constraints in the C-terminal loop further increase the active site rigidity and limit conformational ensemble. Collectively, these structural distinctions lower protein plasticity and change the heme environment, which, in turn, could impede the spin-state transition essential for optimal reactivity and oxidation of substrates.


Assuntos
Citocromo P-450 CYP3A/química , Ligantes , Sequência de Aminoácidos , Aminoácidos , Sítios de Ligação , Catálise , Domínio Catalítico , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Humanos , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Mutação , Polimorfismo Genético , Ligação Proteica , Relação Estrutura-Atividade , Especificidade por Substrato
9.
J Pak Med Assoc ; 71(4): 1175-1180, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34125766

RESUMO

OBJECTIVE: To investigate the association of receptor for advanced glycation end products gene polymorphism 429T/C (rs1800625) with diabetic retinopathy and serum soluble receptor for advanced glycation end products levels in patients with type 2 diabetes. METHODS: The case-control study was conducted from January 2017 to December 2018 at Pakistan Railway Hospital, Rawalpindi, and the Multidisciplinary Laboratories of Islamic International Medical College, Riphah International University (RIU), Islamabad, Pakistan. Those included were healthy controls in group A, diabetics without retinopathy in group B and patients having diabetic retinopathy in group C. Genotyping for 429T/C was done by tetra-primer amplification refractory mutation system-polymerase chain reaction. Serum soluble receptor for advanced glycation end products levels were measured using enzyme-linked immunosorbent assay. Data was analysed using SPSS 22. RESULTS: Of the 450 subjects, 150(33.3%) were in each of the three groups. The frequency of TT, TC and CC genotypes of 429T/C polymorphism were 137(91.3%), 10(6.7%) and 3(2%) in group A; 133(88.6%), 13(8.7%) and 4(2.7%) in group B; and 127(84.7%), 18(12%) and 5(3.3%) in group C. No significant association of 429T/C genotypic and allelic frequencies were found with groups B and C (p>0.05). Serum soluble receptor for advanced glycation end products levels were significantly high in patients with proliferative diabetic retinopathy and were positively correlated with fasting plasma glucose in group C (p<0.05). TC and CC genotypes were significantly associated with raised serum soluble receptor for advanced glycation end products, and TC with raised fasting plasma glucose in group C. CONCLUSIONS: The 429T/C receptor for advanced glycation end products gene polymorphism was found to be associated with severe non-proliferative diabetic retinopathy, and serum soluble receptor for advanced glycation end products levels had a positive correlation with severity of diabetic retinopathy.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Receptor para Produtos Finais de Glicação Avançada , Antígenos de Neoplasias , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/genética , Retinopatia Diabética/genética , Produtos Finais de Glicação Avançada , Humanos , Proteínas Quinases Ativadas por Mitógeno , Paquistão , Polimorfismo Genético , Receptor para Produtos Finais de Glicação Avançada/sangue , Receptor para Produtos Finais de Glicação Avançada/genética , Receptores Imunológicos/genética
10.
Sci Rep ; 11(1): 13300, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-34172780

RESUMO

Nucleotide-binding domain and leucine-rich repeat (LRR)-containing family protein 3 (NLRP3) regulated the maturation of inflammation-related cytokines by forming NLRP3 inflammasome, which plays pivotal roles in sepsis pathogenesis. In this study, we evaluated the genetic association of NLRP3 polymorphisms with sepsis (640 patients and 769 controls) and characterized the impact of NLRP3 polymorphisms on NLRP3 expression and inflammatory responses. No significant differences were observed in genotype/allelic frequencies of NLRP3 29940G>C between sepsis cases and controls. The G allele was significantly overrepresented in patients with septic shock than those in sepsis subgroup, and the GC/GG genetypes were related to the 28-day mortality of sepsis. Lipopolysaccharide challenge to peripheral blood mononuclear cells showed a significant suppression of NLRP3 mRNA expression and release of IL-1ß and TNF-α in CC compared with the GC/GG genotype category. Functional experiments with luciferase reporter vectors containing the NLRP3 3'-UTR with the 29940 G-to-C variation in HUVECs and THP-1 cells showed a potential suppressive effect of miR-146a on NLRP3 transcription in the presence of the C allele. Taken together, these results demonstrated that the 29940 G-to-C mutation within the NLRP3 3'-UTR was a gain-of-function alteration that caused the suppression of NLRP3 expression and downstream inflammatory cytokine production via binding with miR-146a, which ultimately protected patients against susceptibility to sepsis progression and poor clinical outcome.


Assuntos
MicroRNAs , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Sepse , China/epidemiologia , Citocinas/metabolismo , Progressão da Doença , Suscetibilidade a Doenças , Feminino , Mutação com Ganho de Função , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamassomos/metabolismo , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Polimorfismo Genético , Sepse/epidemiologia , Sepse/genética , Células THP-1
11.
Biomed Khim ; 67(3): 213-221, 2021 May.
Artigo em Russo | MEDLINE | ID: mdl-34142528

RESUMO

To search for new targets of therapy, it is necessary to reconstruct the gene network of the disease, and identify the interaction of genes, proteins, and drug compounds. Using the online bioinformatics tools we have analyzed the current data set related to the metabolism of xenobiotics, mediated by the N-acetyltransferase 2 (NAT2) gene. The study of allelic polymorphism of the NAT2 gene has a prognostic value, allowing to determine the risk of a number of oncological diseases, the degree of increased risk due to smoking and exposure to chemical carcinogens, including drugs. The aim of this study was to determine the frequencies of two important "slow" variants of the NAT2 gene (NAT2*5, rs1801280 and NAT2*7, rs1799931), which significantly affected the rate of xenobiotic acetylation among the indigenous Nenets population of Northern Siberia. The obtained frequencies of polymorphic variants among the Nenets occupy an intermediate value between those for Europeans and Asians, which might indicate specific features of adaptation. We present a model of the distribution of two polymorphic variants of the NAT2 gene involved in the biotransformation of xenobiotics to study the characteristics of their metabolism in the indigenous inhabitants of Yamal.


Assuntos
Arilamina N-Acetiltransferase , Acetilação , Alelos , Arilamina N-Acetiltransferase/genética , Arilamina N-Acetiltransferase/metabolismo , Redes Reguladoras de Genes , Humanos , Polimorfismo Genético
12.
Medicine (Baltimore) ; 100(26): e26104, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190143

RESUMO

ABSTRACT: Thirty-five previous meta-analyses have been reported on the individual glutathione S-transferase M1 (GSTM1) present/null, glutathione S-transferase T1 (GSTT1) present/null, and glutathione S-transferase P1 (GSTP1) IIe105Val polymorphisms with lung cancer (LC) risk. However, they did not appraise the credibility and explore the combined effects between the 3 genes and LC risk.We performed a meta-analysis and re-analysis of systematic previous meta-analyses to solve the above problems.Meta-analyses of Observational Studies in Epidemiology guidelines were used. Moreover, we employed false-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and the Venice criteria to verify the credibility of current and previous meta-analyses.Significantly increased LC risk was considered as "highly credible" or "positive" for GSTM1 null genotype in Japanese (odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.17-1.44, I2 = 0.0%, statistical power = 0.997, FPRP = 0.008, BFDP = 0.037, and Venice criteria: AAB), for GSTT1 null genotype in Asians (OR = 1.23, 95% CI = 1.12-1.36, I2 = 49.1%, statistical power = 1.000, FPRP = 0.051, BFDP = 0.771, and Venice criteria: ABB), especially Chinese populations (OR = 1.31, 95% CI = 1.16-1.49, I2 = 48.9%, Statistical power = 0.980, FPRP = 0.039, BFDP = 0.673, and Venice criteria: ABB), and for GSTP1 IIe105Val polymorphism in Asians (Val vs IIe: OR = 1.28, 95% CI = 1.17-1.42, I2 = 30.3%, statistical power = 0.999, FPRP = 0.003, BFDP = 0.183, and Venice criteria: ABB). Significantly increased lung adenocarcinoma (AC) risk was also considered as "highly credible" or "positive" in Asians for the GSTM1 (OR = 1.35, 95% CI = 1.22-1.48, I2 = 25.5%, statistical power = 0.988, FPRP < 0.001, BFDP < 0.001, and Venice criteria: ABB) and GSTT1 (OR = 1.36, 95% CI = 1.17-1.58, I2 = 30.2%, statistical power = 0.900, FPRP = 0.061, BFDP = 0.727, and Venice criteria: ABB) null genotype.This study indicates that GSTM1 null genotype is associated with increased LC risk in Japanese and lung AC risk in Asians; GSTT1 null genotype is associated with increased LC risk in Chinese, and GSTP1 IIe105Val polymorphism is associated with increased LC risk in Asians.


Assuntos
Adenocarcinoma/genética , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Neoplasias Pulmonares/genética , Polimorfismo Genético , Genótipo , Humanos , Fatores de Risco
13.
Toxins (Basel) ; 13(5)2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064406

RESUMO

Ribosome-inactivating proteins (RIPs) are toxic proteins that can inhibit protein synthesis. RIPs purified from Bougainvillea have low nonspecific toxicity, showing promise for processing applications in the agricultural and medical fields. However, systematic research on the polymorphism of Bougainvillea RIPs is lacking, and it is worth exploring whether different isoforms differ in their active characteristics. The transcriptional and translational expression of type I RIPs in Bougainvillea glabra leaves was investigated in this study. Seven RIPs exhibited seasonal variation at both the mRNA and protein levels. The isoforms BI4 and BI6 showed the highest transcriptional expression in both the summer and autumn samples. Interestingly, BI6 was not detected in the protein level in any of the samples. However, the bioinformatics analysis showed that RIPs derived from the same species were gathered in a different cluster, and that the active sites changed among the isoforms during evolution. The significant discrepancy in Bougainvillea RIPs mainly locates at both termini of the amino acid sequence, particularly at the C terminus. Post-translational modifications may also exist in Bougainvillea RIPs. It is concluded that the reason for the polymorphism of Bougainvillea RIPs may be that these proteins are encoded by multiple genes due to genetic processes such as gene duplication and mutation. According to the results of sequence analysis, the possible functional differences of B. glabra RIP isoforms are discussed with regard to the observed discrepancy in both active sites and structures.


Assuntos
Nyctaginaceae/metabolismo , Proteínas de Plantas/genética , Proteínas Inativadoras de Ribossomos/genética , Sequência de Aminoácidos , Domínio Catalítico , Nyctaginaceae/genética , Folhas de Planta , Polimorfismo Genético , Biossíntese de Proteínas
14.
Epilepsy Behav ; 121(Pt A): 108088, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34102472

RESUMO

OBJECTIVE: To explore the role of several genetic polymorphisms (APOE ε4, BDNF Met, and COMT Val) in executive functioning performance in patients with pharmacoresistant temporal lobe epilepsy (TLE). METHODS: Ninety-three adults (51 female, mean age = 39 years) with TLE completed executive functioning measures as part of a comprehensive preoperative neuropsychological evaluation, including Trail Making Test (Part B), Wisconsin Card Sorting Test (Conceptual Level Responses and Perseverative Errors), Color Word Interference from the Delis Kaplan Executive Function System, and measures of phonemic and semantic verbal fluency. Genotyping of the APOE, BDNF, and COMT genes was conducted using DNA extracted from peripheral blood or brain tissue (from epilepsy surgery). RESULTS: After adjustment for general cognitive ability, COMT Val carriers showed poorer performance on semantic verbal fluency and color word interference than non-carriers, and BDNF Met carriers showed poorer performance on phonemic verbal fluency than those without a Met allele. SIGNIFICANCE: Results suggest that COMT and BDNF polymorphisms are associated with performance on several EF measures in patients with TLE, including tasks assessing verbal fluency and response inhibition and account for up to 16% of the variance in test performance. The APOE polymorphism was not significantly associated with any of the executive function measures analyzed.


Assuntos
Epilepsia do Lobo Temporal , Função Executiva , Adulto , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/genética , Feminino , Humanos , Testes Neuropsicológicos , Polimorfismo Genético/genética , Teste de Sequência Alfanumérica
15.
Int J Mol Sci ; 22(9)2021 May 08.
Artigo em Inglês | MEDLINE | ID: covidwho-1224029

RESUMO

The elderly and patients with several comorbidities experience more severe cases of coronavirus disease 2019 (COVID-19) than healthy patients without underlying medical conditions. However, it is unclear why these people are prone to developing alveolar pneumonia, rapid exacerbations, and death. Therefore, we hypothesized that people with comorbidities may have a genetic predisposition that makes them more vulnerable to various factors; for example, they are likely to become more severely ill when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To test this hypothesis, we searched the literature extensively. Polymorphisms of genes, such as those that encode angiotensin-converting enzyme 1 (ACE1), have been associated with numerous comorbidities, such as cardiovascular disease, hypertension, diabetes, chronic kidney disease, and obesity, and there are potential mechanisms to explain these associations (e.g., DD-type carriers have greater ACE1 activity, and patients with a genetic alpha-1 anti-trypsin (AAT) deficiency lack control over inflammatory mediators). Since comorbidities are associated with chronic inflammation and are closely related to the renin-angiotensin-aldosterone system (RAAS), these individuals may already have a mild ACE1/ACE2 imbalance before viral infection, which increases their risk for developing severe cases of COVID-19. However, there is still much debate about the association between ACE1 D/I polymorphism and comorbidities. The best explanation for this discrepancy could be that the D allele and DD subtypes are associated with comorbidities, but the DD genotype alone does not have an exceptionally large effect. This is also expected since the ACE1 D/I polymorphism is only an intron marker. We also discuss how polymorphisms of AAT and other genes are involved in comorbidities and the severity of SARS-CoV-2 infection. Presumably, a combination of multiple genes and non-genetic factors is involved in the establishment of comorbidities and aggravation of COVID-19.


Assuntos
COVID-19/genética , Predisposição Genética para Doença , Peptidil Dipeptidase A/genética , Idoso , Alelos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/metabolismo , COVID-19/fisiopatologia , COVID-19/virologia , Comorbidade , Antígenos HLA/genética , Antígenos HLA/metabolismo , Haplótipos , Humanos , Inflamação/genética , Inflamação/metabolismo , Homem de Neandertal/genética , Peptidil Dipeptidase A/metabolismo , Polimorfismo Genético , Fatores de Risco , Índice de Gravidade de Doença
16.
Hum Immunol ; 82(8): 551-560, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: covidwho-1265675

RESUMO

Given the highly polymorphic nature of Human Leukocyte Antigen (HLA) molecules, it is not surprising that they function as key regulators of the host immune response to almost all invading pathogens, including SARS-CoV-2, the etiological agent responsible for the recent COVID-19 pandemic. Several correlations have already been established between the expression of a specific HLA allele/haplotype and susceptibility/progression of SARS-CoV-2 infection and new ones are continuously emerging. Protective and harmful HLA variants have been described in both mild and severe forms of the disease, but considering the huge amount of existing variants, the data gathered in such a brief span of time are to some extent confusing and contradictory. The aim of this mini-review is to provide a snap-shot of the main findings so far collected on the HLA-SARS-CoV-2 interaction, so as to partially untangle this intricate yarn. As key factors in the generation of antigenic peptides to be presented by HLA molecules, ERAP1 and ERAP2 role in SARS-CoV-2 infection will be revised as well.


Assuntos
Aminopeptidases/genética , Apresentação do Antígeno , Antígenos Virais/imunologia , COVID-19/genética , Antígenos HLA/genética , Antígenos de Histocompatibilidade Menor/genética , Polimorfismo Genético , SARS-CoV-2/imunologia , Aminopeptidases/imunologia , Animais , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/virologia , Epitopos , Antígenos HLA/imunologia , Interações Hospedeiro-Patógeno , Humanos , Antígenos de Histocompatibilidade Menor/imunologia , SARS-CoV-2/patogenicidade
17.
Ann Palliat Med ; 10(6): 6518-6534, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34154362

RESUMO

BACKGROUND: Isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) are the four most common drugs for the first-line treatment of tuberculosis (TB). Although chemotherapy drugs are widely used in the treatment of TB, and achieved good results, but the side effects, especially anti-tuberculosis drug-induced liver injury (ATDILI), cannot be overlooked. Many researchers have made efforts to uncover the association of cytochrome P450 (CYP) enzyme genetic polymorphisms with ATDILI. In this study, we systematically reviewed and meta-analyzed the relationship between CYP polymorphism and susceptibility to ATDILI. METHODS: We carried out literature searches of PubMed, Ovid, the Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure (CNKI). Medical Subject Headings (MeSH) terms including "cytochrome P450 enzyme", "drug-induced liver injury", "polymorphism", "tuberculosis", and "hepatotoxicity" were used as keywords for our searches. RESULTS: The pooled odds ratio (OR) of all studies for CYP2E1 to the risk of ATDILI was 1.18 [95% confidence interval (CI): 0.82-1.71]. The articles in this meta-analysis were observed to be mildly heterogeneous. Further subgroup analysis revealed that the patients who receiving a four-drug protocol (INH + RIF + PZA + EMB) or three-drug protocol (INH + RIF + PZA) regimens showed a higher risk of ATDILI than those who receiving INH alone. However, subgroup analyses according to participants' ethnic origin, study type, and the definition of ATDILI produced no statistically significant results. Associations between other genes in the CYP family and ATDILI were indistinct and equivocal. DISCUSSION: Our meta-analysis has uncovered an association between CYP2E1 RsaI/PstI polymorphisms and ATDILI, especially among patients who receive a four-drug (INH + RIF + PZA + EMB) or three-drug (INH + RIF + PZA) anti-TB treatment regimen.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Tuberculose , Antituberculosos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/genética , Sistema Enzimático do Citocromo P-450/genética , Humanos , Polimorfismo Genético/genética , Tuberculose/tratamento farmacológico
18.
Ann Saudi Med ; 41(3): 141-146, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1261414

RESUMO

BACKGROUND: Angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism may play a role in the pathogenesis of coronavirus-19 disease (COVID-19). OBJECTIVES: Investigate the relationship between ACE I/D polymorphism and the clinical severity of COVID-19. DESIGN: Prospective cohort study. SETTING: Tertiary care hospital. PATIENTS AND METHODS: The study included COVID-19 patients with asymptomatic, mild, and severe disease with clinical data and whole blood samples collected from 1 April 2020 to 1 July 2020. ACE I/D genotypes were determined by polymerase chain reaction and agarose gel electrophoresis. MAIN OUTCOME MEASURE: ACE DD, DI and II genotypes frequencies. SAMPLE SIZE: 90 cases, 30 in each disease severity group. RESULTS: Age and the frequency of general comorbidity increased significantly from the asymptomatic disease group to the severe disease group. Advanced age, diabetes mellitus and presence of ischemic heart disease were independent risk factors for severe COVID-19 [OR and 95 % CI: 1.052 (1.021-1.083), 5.204 (1.006-26.892) and 5.922 (1.109-31.633), respectively]. The ACE II genotype was the dominant genotype (50%) in asymptomatic patients, while the DD genotype was the dominant genotype (63.3 %) in severe disease. The ACE II geno-type was protective against severe COVID-19 [OR and 95% CI: .323 (.112-.929)]. All nine patients (8.9%) who died had severe disease. CONCLUSIONS: The clinical severity of COVID-19 infection may be associated with the ACE I/D polymorphism. LIMITATIONS: Small sample size and single center. CONFLICT OF INTEREST: None.


Assuntos
COVID-19/genética , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Índice de Gravidade de Doença , Adulto , Idoso , Sequência de Bases , COVID-19/diagnóstico , Feminino , Seguimentos , Marcadores Genéticos , Genótipo , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Mutagênese Insercional , Estudos Prospectivos , Deleção de Sequência
19.
Fa Yi Xue Za Zhi ; 37(2): 145-150, 2021 Apr.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34142473

RESUMO

Abstract: Objective To investigate the correlation between the polymorphism of 4 coagulation-related genes, rs1799963 (coagulation factor V gene Leiden), rs6025 (prothrombin gene G20210A), rs1042579 (thrombomodulin protein gene c.1418C>T) and rs1801131 (methylenetetrahydroflate reductase gene) and lower extremity deep venous thrombosis (LEDVT). Methods The 4 genotypes mentioned above of 150 LEDVT patients and 153 healthy controls were detected by the kompetitive allele specific polymerase chain reaction (KASP), then related blood biochemical indicators were collected, binary Logistic regression was established to screen the independent risk factors of LEDVT, and the correlation between polymorphism of 4 coagulation-related genes and LEDVT and its indicators under different genetic modes after adjusting confounding factors were analyzed. Results Five variables, D-dimer, fibrinogen degradation product, homocysteine, sex and age might be the risk factors of LEDVT. These variables were put into 4 genetic inheritance models, and adjusted in binary Logistic regression. The results suggested that the mutations of rs1042579 were correlated with LEDVT under dominant inheritance mode. Conclusion The gene polymorphism of rs1799963, rs6025 and rs1801131 has no significant correlation with the formation of LEDVT. The gene polymorphism of rs1042579 plays a role under dominant inheritance mode, and might be an independent risk factor for formation of LEDVT.


Assuntos
Trombose Venosa , Coagulação Sanguínea/genética , Humanos , Extremidade Inferior , Polimorfismo Genético , Fatores de Risco , Trombose Venosa/genética
20.
J Pak Med Assoc ; 71(5): 1332-1336, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34091609

RESUMO

Objectives: To find the association between interleukin-1 receptor-associated kinase 1 rs3027898 gene polymorphism and preeclampsia. METHODS: The case-control study was conducted from October, 2018 to September, 2019 at the Railway General Hospital and the Department of Biochemistry, Islamic International Medical College, Rawalpindi, Pakistan, and comprised patients diagnosed with preeclampsia and healthy controls. The interleukin receptor-associated kinase-1 polymorphism was determined using multiplex tetra primer amplification refractory mutation system polymerase chain reaction. Outcomes were determined in terms of association of interleukin receptor-associated kinase-1 with preeclampsia. Data was analysed using SPSS 22. RESULTS: Of the 160 subjects, 80(50% were cases with a mean age of 30±5.3 years and 80(50%) were controls with a mean age of 27±3.7 years. AC genotype was seen in 45(56.25%) cases and 30(37.5%) controls, AA genotype in 25(31.25%) cases and 30(37.5%) controls, while CC genotype was seen in 10(12.5%) cases and 20(25%) controls (p>0.05). CONCLUSIONS: There was no significant association of interleukin receptor-associated kinase-1 genotypes with preeclampsia.


Assuntos
Pré-Eclâmpsia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Quinases Associadas a Receptores de Interleucina-1 , Paquistão/epidemiologia , Polimorfismo Genético , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/genética , Gravidez , Receptores de Interleucina-1 , Adulto Jovem
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