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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.
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
3.
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
4.
Gene ; 791: 145709, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33984442

RESUMO

Cervical cancer is the second most diagnosed cancer in Moroccan women. The main etiological factor for developing cervical cancer is the persistent infection with HPV16. Genetic studies have reported the occurrence of amino acid variations within the E6 oncoprotein that promotes host cell transformation by targeting p53 for degradation. To verify the biological effects of E6 polymorphisms towards p53 degradation, HPV16-E6 prototype and 7 variants isolated from cervical cancer biopsies of Moroccan women were evaluated for their activities by transient expression assays using pcDNA3.1-E6 constructs in C33A cell line. Expression of E6 genes in transfected cells was detected with reverse transcription PCR (RT-PCR), then, p53 levels were evaluated by western blot analysis. Significant dissimilarities in p53 degradation activities of HPV16-E6 prototype and intratypic variants were noticed. As compared to the prototype, the highest p53 degradation were exhibited by the African variants Af2-a/r, Af1-d/G295 and Af2-a/G285 (p < 0.001), followed by the European variants E- C442/G350 and E-G350/r (p < 0.01), then, the North American variant NA1-b/r (p < 0.05). The inter-variant differences were statistically significant between Af2-a/r variant and the North American variants NA1-b/r and NA1 (p < 0.05). Thus, the Af2-a/r variant was significantly more active in degrading p53 in our in vitro experiments (p < 0.0001). Our findings support the fact that HPV16-E6 variations have a biological impact on degrading p53, and so, represent a significant carcinogenic potential for developing cervical cancer.


Assuntos
Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adulto , Idoso , Linhagem Celular , Feminino , Variação Genética/genética , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/metabolismo , Humanos , Pessoa de Meia-Idade , Marrocos/epidemiologia , Mutação/genética , Infecções por Papillomavirus/genética , Polimorfismo Genético/genética , Proteína Supressora de Tumor p53/genética , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/virologia
6.
Int J Mol Sci ; 22(9)2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33926081

RESUMO

Guanine-rich DNA sequences self-assemble into highly stable fourfold structures known as DNA-quadruplexes (or G-quadruplexes). G-quadruplexes have furthermore the tendency to associate into one-dimensional supramolecular aggregates termed G-wires. We studied the formation of G-wires in solutions of the sequences d(G4C2)n with n = 1, 2, and 4. The d(G4C2)n repeats, which are associated with some fatal neurological disorders, especially amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), represent a challenging research topic due to their extensive structural polymorphism. We used dynamic light scattering (DLS) to measure translational diffusion coefficients and consequently resolve the length of the larger aggregates formed in solution. We found that all three sequences assemble into longer structures than previously reported. The d(G4C2) formed extremely long G-wires with lengths beyond 80 nm. The d(G4C2)2 formed a relatively short stacked dimeric quadruplex, while d(G4C2)4 formed multimers corresponding to seven stacked intramolecular quadruplexes. Profound differences between the multimerization properties of the investigated sequences were also confirmed by the AFM imaging of surface films. We propose that π-π stacking of the basic G-quadruplex units plays a vital role in the multimerization mechanism, which might be relevant for transformation from the regular medium-length to disease-related long d(G4C2)n repeats.


Assuntos
Expansão das Repetições de DNA/genética , DNA/química , Quadruplex G , Esclerose Amiotrófica Lateral/genética , Dicroísmo Circular , Citosina , DNA/genética , Expansão das Repetições de DNA/fisiologia , Demência Frontotemporal/genética , Guanina , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação de Ácido Nucleico , Polimorfismo Genético/genética
7.
Medicine (Baltimore) ; 100(17): e25487, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907097

RESUMO

BACKGROUD: To analyze the correlation between gene polymorphisms of 5,10- methylenetetrahydrofolate reductase (MTHFR) and risk of unexplained recurrent pregnancy loss (URPL) in Chinese women. METHODS: Eligible studies were searched in Pubmed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) databases. Established inclusion criteria were used to screening articles, subsequently evaluate the quality of the included studies, Stata 16.0 PM and RevMan 5.3 software were conducted for meta-analysis. The pooled odds ratio (OR) with 95% confidence interval (CI) was determined to assess the relationship between MTHFR and risk of URPL in Chinese women. RESULTS: For MTHFR C677T, fifty studies were included, involving 6677 URPL cases and 8111 controls. The overall results showed that MTHFR C677T was significantly correlated with URPL risk, especially in the homozygous model (TT vs CC; OR 3.06; 95% CI 2.56-3.66). For MTHFR A1298C, twenty-first studies were included, involving 3439 URPL cases and 3155 controls. The results showed that MTHFR A1298C was also significantly correlated with URPL risk in recessive (CC vs AC + AA; OR 1.55; 95% CI 1.25-1.93) and homozygous (CC vs AA; OR 1.53; 95% CI 1.22-1.91) models. In addition, sub-group results showed that no significant difference between north and south China populations in the MTHFR gene polymorphisms and URPL risk. Of note, the patients carrying MTHFR C677T and MTHFR A1298C joint mutants had no synergistic effect (OR 2.71; 95% CI 0.84-8.70) on the occurrence of URPL compared with the wild-type homozygous genotype (MTHFR 677CC/ MTHFR 1298AA). CONCLUSION: Studies included in this meta-analysis suggested that MTHFR 677T allele and 677TT genotype and MTHFR 1298CC genotype were both associated with URPL; testing MTHFR C677T gene polymorphism was a more appropriate target compared with other mutations in the prediction of URPL.


Assuntos
Aborto Habitual/genética , Predisposição Genética para Doença/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético/genética , Aborto Habitual/etnologia , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Feminino , Genótipo , Humanos , Razão de Chances , Gravidez , Fatores de Risco
8.
Gynecol Obstet Invest ; 86(1-2): 177-184, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33895751

RESUMO

OBJECTIVES: Insulin receptor substrate 1 (IRS1) is a crucial factor in the insulin signaling pathway. IRS1 gene polymorphism rs1801278 in mothers has been reported to be associated with gestational diabetes mellitus (GDM). However, it is not clear whether IRS1 gene polymorphism rs1801278 in fetuses is associated with their mothers' GDM morbidity. The purpose of this study is to analyze the association between maternal, fetal, or maternal/fetal IRS1 gene polymorphism rs1801278 and GDM risk. DESIGN: The study was a single-center, prospective cohort study. In total, 213 pairs of GDM mothers/fetuses and 191 pairs of control mothers/fetuses were included in this study. They were recruited after they underwent oral glucose tolerance test during 24-28 weeks of gestation and followed up until delivery. All participants received the conventional interventions (diet and exercise), and no special therapy except routine treatment. METHODS: A total of 213 pairs of GDM mothers/fetuses and 191 pairs of normal blood glucose pregnant mothers/fetuses were ge-notyped using PCR and DNA sequencing from January 2015 to September 2016. Maternal/fetal IRS1 gene polymorphism rs1801278 was analyzed and compared between 2 groups. RESULTS: There were no significant differences in the frequency of individual mothers' or fetuses' IRS1 rs1801278 polymorphisms between 2 groups; if both the mothers and fetuses carried A allele, significantly lower GDM morbidity was observed in the mothers. LIMITATIONS: The sample size was relatively small as a single-center study. CONCLUSIONS: Our study suggested that maternal/fetal rs1801278 polymorphism of IRS1 is a modulating factor in GDM; both mothers/fetuses carrying the A allele of rs1801278 may protect the mothers against the development of GDM.


Assuntos
Diabetes Gestacional/genética , Feto , Proteínas Substratos do Receptor de Insulina/genética , Polimorfismo Genético/genética , Adulto , Alelos , China , DNA/sangue , Feminino , Frequência do Gene , Genótipo , Idade Gestacional , Teste de Tolerância a Glucose , Humanos , Insulina , Gravidez , Cuidado Pré-Natal , Estudos Prospectivos , Análise de Sequência de DNA
9.
Medicine (Baltimore) ; 100(15): e25530, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33847678

RESUMO

OBJECTIVE: The present study aimed to conduct a systematic review and meta-analysis to evaluate the relationships between ATP2B1 gene polymorphisms with blood pressure (BP) level and susceptibility to hypertension. METHODS: PubMed, Web of Science, Embase and China National Knowledge Infrastructure (CNKI) Databases were systematically searched by 2 independent researchers to screen studies on ATP2B1 gene polymorphisms and BP related phenotypes. The records retrieval period was limited from the formation of the database to March 4, 2021. Pooled odds rations (ORs) or ß and their 95% confidence intervals (95%CI) were calculated to assess the association between ATP2B1 gene polymorphisms and the risk of hypertension or BP levels. Publication bias and sensitivity analysis were conducted to find potential bias. All the statistical analysis were conducted with Stata version 11.0 software. RESULTS: A total of 15 articles were ultimately included in the present study, including 15 polymorphisms of ATP2B1 gene. Nine articles (N = 65,362) reported the polymorphism rs17249754, and 7 articles(N = 91,997) reported rs2681472 (both loci were reported in 1 article). Meta-analysis showed that rs17249754 (G/A) and rs2681472 (A/G) were associated with the susceptibility to hypertension (rs17249754: OR = 1.19, 95%CI: 1.10-1.28; rs2681472: OR = 1.15, 95%CI: 1.12-1.17), and were positively associated with systolic BP (SBP) and diastolic blood pressure (DBP) (rs17249754: SBP, ß=1.01, 95%CI: 0.86-1.16, DBP, ß=0.48, 95%CI: 0.30-0.66; rs2681472: SBP, ß=0.92, 95%CI: 0.77-1.07, DBP, ß=0.50, 95%CI: 0.42-0.58) in the additive genetic model. Subgroup analysis stratified by race, population, sample size, and BP measurement method revealed that the association between A allele in rs2681472 polymorphism and risk of hypertension was slightly stronger in European (EUR) populations (OR = 1.16, 95%CI: 1.13-1.20) than in East Asians (OR = 1.14, 95%CI: 1.10-1.17). While in East Asians, relation between rs17249754 with risk of hypertension (OR = 1.19, 95%CI: 1.10-1.28) is stronger than rs2681472 (OR = 1.14, 95%CI: 1.10-1.17). CONCLUSIONS: Our study demonstrated that ATP2B1 gene polymorphism rs2681472 and rs17249754 were associated with BP levels and the susceptibility to hypertension.


Assuntos
Pressão Sanguínea/genética , Predisposição Genética para Doença/genética , Hipertensão/genética , ATPases Transportadoras de Cálcio da Membrana Plasmática/genética , Polimorfismo Genético/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo
10.
Medicine (Baltimore) ; 100(12): e25078, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761666

RESUMO

BACKGROUND: Breast cancer is one of the common malignant tumors in women, which seriously affects women's physical and mental health and even life-threatening. The occurrence and development of breast cancer are closely related to genetic factors. Many studies have shown that human leukocyte antigen DRB1 is associated with the development of breast cancer, but lack evidence. This study aims to systematically evaluate the relationship between HLA-DRB1 gene polymorphism and breast cancer. METHODS: The retrieval time of this study was from the establishment of the database to February 2021. The retrieval databases included CNKI, Wanfang, VIP and China Biomedical Database, PubMed, Embase, Web of Science, and the Cochrane Library. The retrieval objects were observational studies on the relationship between HLA-DRB1 gene polymorphism and breast cancer (including case--control studies, cross-sectional studies, and cohort studies). The language restrictions were English and Chinese. Two researchers independently extracted the data and assessed the quality of the included studies, and Stata 16.0 software was used for statistical analysis. RESULTS: This study will systematically evaluate the relationship between HLA-DRB1 gene polymorphism and breast cancer based on existing studies. CONCLUSION: This study will explore the early warning signal of breast cancer genetic susceptibility, and provide evidence-based medical evidence for clarifying the role of HLA-DRB1 gene polymorphism in breast cancer. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/847FQ.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Cadeias HLA-DRB1/genética , Polimorfismo Genético/genética , Biomarcadores Tumorais/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Metanálise como Assunto , Estudos Observacionais como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
11.
Medicine (Baltimore) ; 100(12): e25146, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761682

RESUMO

BACKGROUND: Previous epidemiological studies displayed that long non-coding RNA (LncRNA) polymorphisms are associated with an increased risk of coronary artery disease, while the results are inconsistent. Therefore, we conducted a meta-analysis to more accurately determine the association between LncRNA polymorphism and the risk of coronary artery disease. METHODS: PubMed, EmBase and Web of Science databases were searched, and the time to build the database was set until December 2020. The association between LncRNA polymorphism and the risk of coronary artery disease was collected and evaluated. Meta-analysis was performed by STATA 14.0 software, and the odds ratio and its 95% confidence interval (95%CI) were applied to estimate the association between LncRNA polymorphism and the risk of coronary artery disease. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This meta-analysis will summarize the relationship between LncRNA polymorphism and coronary disease risk. ETHICS AND DISSEMINATION: Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/9XPHS.


Assuntos
Doença da Artéria Coronariana/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , RNA Longo não Codificante/genética , Estudos de Casos e Controles , Fatores de Risco de Doenças Cardíacas , Humanos , Metanálise como Assunto , Razão de Chances , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
12.
J Nutr Health Aging ; 25(4): 410-415, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33786555

RESUMO

OBJECTIVE: Frailty is known to be influenced by genetics, however, little evidence on the association of Apolipoprotein E (ApoE) genotype and frailty exists which we aim to investigate. DESIGN: This study is a cross-sectional analysis from a prospective longitudinal study cohort. SETTING AND PARTICIPANTS: Community-dwelling individuals aged 55 years and older from Beijing region in China. MEASUREMENTS: A total of 3,569 older adults with a mean age of 75.06(±6.79) years were included. We investigated the association between ApoE polymorphism and frailty syndrome using the frailty index (FI) and frailty phenotype (including association with individual components of the frailty phenotype). Logistic regressions were performed to investigate the relation between ApoE variants and frailty. RESULTS: There was no significant association between ApoE variants and frailty as assessed by the FI. In the age and sex-adjusted model, compared to the ApoE e3/e3 carriers ApoE e4 carriers had almost 1.5 times higher odds of being frail as assessed by the frailty phenotype. However, the significance was lost on the model with adjustment for cognitive impairment. Compared to the ApoE e3/e3 carriers ApoE e4 carriers had almost two times higher odds of fatigue. ApoE e4 heterozygotes had higher odds of fatigue compared to ApoE e4 non-carriers. No significant association was found between ApoE variants and other components of frailty phenotype. CONCLUSIONS: Our findings do not support an association between ApoE genotype and frailty irrespective of the frailty assessment tools. Fatigue in older adults is the only component of frailty phenotype influenced by ApoE genotype.


Assuntos
Apolipoproteínas E/genética , Fadiga/genética , Idoso Fragilizado/estatística & dados numéricos , Fragilidade/genética , Polimorfismo Genético/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos Transversais , Fadiga/fisiopatologia , Feminino , Humanos , Vida Independente , Estudos Longitudinais , Masculino , Estudos Prospectivos
13.
Am J Hum Genet ; 108(3): 517-524, 2021 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-33667394

RESUMO

Tuberculosis (TB), usually caused by Mycobacterium tuberculosis bacteria, is the first cause of death from an infectious disease at the worldwide scale, yet the mode and tempo of TB pressure on humans remain unknown. The recent discovery that homozygotes for the P1104A polymorphism of TYK2 are at higher risk to develop clinical forms of TB provided the first evidence of a common, monogenic predisposition to TB, offering a unique opportunity to inform on human co-evolution with a deadly pathogen. Here, we investigate the history of human exposure to TB by determining the evolutionary trajectory of the TYK2 P1104A variant in Europe, where TB is considered to be the deadliest documented infectious disease. Leveraging a large dataset of 1,013 ancient human genomes and using an approximate Bayesian computation approach, we find that the P1104A variant originated in the common ancestors of West Eurasians ∼30,000 years ago. Furthermore, we show that, following large-scale population movements of Anatolian Neolithic farmers and Eurasian steppe herders into Europe, P1104A has markedly fluctuated in frequency over the last 10,000 years of European history, with a dramatic decrease in frequency after the Bronze Age. Our analyses indicate that such a frequency drop is attributable to strong negative selection starting ∼2,000 years ago, with a relative fitness reduction on homozygotes of 20%, among the highest in the human genome. Together, our results provide genetic evidence that TB has imposed a heavy burden on European health over the last two millennia.


Assuntos
DNA Antigo/análise , Polimorfismo Genético/genética , TYK2 Quinase/genética , Tuberculose/genética , Restos Mortais , Europa (Continente) , Feminino , Genoma Humano/genética , História Antiga , Humanos , Masculino , Tuberculose/história , Tuberculose/microbiologia
14.
J Equine Vet Sci ; 98: 103358, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33663714

RESUMO

Native breeds are essential for national stocks and genetic reservoir; therefore, the preservation of indigenous breeds is a key policy priority for countries around the world. Many conservationists would assert that genetic diversity is a prerequisite for adaptive evolution, and preserving genetic diversity will need conservation efforts for the long-term survival of domestic species. This study intended to evaluate the genetic diversity of the Iranian Kurdish horse population based on microsatellite indicators, which can partially prevent it from becoming extinct. Fifty-eight tail hair and blood samples were randomly collected from Kurdistan, Kermanshah, Ilam, West Azerbaijan, Isfahan, Kerman, Hamadan, and Tehran. Genomic DNA extraction was performed by a modified salting out method. The polymerase chain reaction amplification conditions were also separately undertaken for each marker. All microsatellite loci revealed polymorphisms in the studied population. Genetic variation was examined using 12 microsatellite loci (HMS7, HMS3, HMS2, HMS6, ASB2, ASB23, VHL20, HTG10, LEX33, ASB17, AHT4, and AHT5). We found that the means of the observed and effective number of alleles were 7.58 and 4.95, with the minimum and maximum values for each of these indices associated with the loci of HMS2 and ASB17, respectively. Moreover, the mean of observed and expected heterozygosity, polymorphism information content, and Shannon's Information Index of the Iranian Kurdish population were 0.77, 0.78, 0.75, and 1.67, respectively, indicating a high degree of genetic diversity in the entire studied population. More specifically, we acquired a range of new alleles in the Iranian Kurdish horse breed that differed in their genetic structure to those of other Iranian breeds in other studies. This study provides an exciting opportunity to improve our knowledge of genetic information which will be beneficial as a base to identify purebred Kurdish horses for a further Iranian Kurdish horse genetic and breeding program.


Assuntos
Repetições de Microssatélites , Polimorfismo Genético , Alelos , Animais , Azerbaijão , Cavalos/genética , Irã (Geográfico) , Repetições de Microssatélites/genética , Polimorfismo Genético/genética
15.
Yonsei Med J ; 62(4): 359-365, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33779090

RESUMO

PURPOSE: Little is known about the relationship between brain-derived neurotrophic factor (BDNF) gene polymorphisms and psychiatric symptoms in diabetes patients. We investigated the effects of BDNF Val/66/Met polymorphism, glucose status, psychological susceptibility, and resilience on anxiety and depression symptoms in patients newly diagnosed with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We examined biochemical factors and BDNF polymorphism in 89 patients who were newly diagnosed with T2DM. Psychiatric symptoms were investigated with the Hospital Anxiety and Depression Scale (HADS), and the Connor-Davidson Resilience Scale (CD-RISC) and Impact of Event Scale (IES) were used to assess psychological resilience and susceptibility to psychological distress, respectively. Logistic regression analyses were conducted to investigate factors associated with psychiatric symptoms. RESULTS: We determined that 62 patients (70%) were Met-carriers. No significant differences were found between the Val/Val homozygous and Met-carrier groups regarding age, sex, body mass index, and clinical factors related to glycemic control and lipid profiles. HADS-anxiety and HADS-depression scores and IES factor scores were higher in the Met-carrier than the Val/Val homozygous group. Hemoglobin A1c (HbA1c) level was significantly inversely correlated with the severity of depressive symptoms. Resilience factors showed significant inverse correlations, and IES factors showed positive correlations with depressive symptom severity. In the logistic regression analysis model, depressive symptoms were significantly associated with HbA1c and BDNF polymorphism, whereas only the hyperarousal factor of the IES scale was associated with anxiety. CONCLUSION: Depressive symptoms are associated with the presence of the Met-carriers and lower HbA1c in patients newly diagnosed with T2DM.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Diabetes Mellitus Tipo 2 , Ansiedade/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Depressão/genética , Diabetes Mellitus Tipo 2/genética , Genótipo , Humanos , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único/genética
16.
Medicine (Baltimore) ; 100(11): e25001, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725974

RESUMO

BACKGROUND: Previous studies displayed that thrombomodulin gene polymorphisms are closely associated with venous thromboembolism (VTE), while the results are inconsistent. Therefore, we conducted a meta-analysis to accurately determine the association between thrombomodulin gene polymorphism and the risk of VTE. METHODS: Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, EmBase, and Web of Science databases were searched, and the time to build the database was set until January 2021. The association between thrombomodulin gene polymorphism and the risk of VTE was evaluated. Meta-analysis was performed with STATA 16.0 software, and the odds ratio and its 95% confidence interval were applied to estimate the relationship between thrombomodulin gene polym'orphism and the risk of VTE. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This meta-analysis will summarize the relationship between thrombomodulin genepolymorphism and VTE risk. ETHICS AND DISSEMINATION: Ethical approval was not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/UEHJP.


Assuntos
Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Trombomodulina/genética , Tromboembolia Venosa/genética , Estudos de Casos e Controles , Genótipo , Humanos , Metanálise como Assunto , Razão de Chances , Projetos de Pesquisa , Fatores de Risco , Revisões Sistemáticas como Assunto
17.
Medicine (Baltimore) ; 100(11): e25113, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725991

RESUMO

BACKGROUND: Recent studies have reported that lncRNA (long noncoding RNAs) antisense non-coding RNA in the INK4 locus (ANRIL) plays important roles in the development of atherosclerosis through regulating cell apoptosis, proliferation, and adhesion. GWAS (genome-wide association studies) identified common genetic variants within ANRIL could confer risk of ischemic stroke (IS) in southern Sweden. METHODS: We performed a case-control study, including 567 IS patients and 552 healthy controls from unrelated northern Chinese Han population, aiming to explore the association between lncRNA ANRIL rs2383207, rs4977574 polymorphisms and the risk of IS. Subsequently we implemented a meta-analysis to further assess the relationship of these variants and the disease. RESULTS: In our case-control study, no significant associations were observed in all models between above 2 polymorphisms and IS. Next in our subgroup analysis, we detected significant association between GA genotype of rs4977574 and the increased risk of LAA-IS (large-artery atherosclerotic ischemic stroke), similar elevated risk also appeared in the GG + GA genotype under the dominant model (P = .048, OR = 1.385, 95% CIs 1.002-1.914; P = .040, OR = 1.378, 95% CIs 1.015-1.872, respectively). As for rs2383207, negative results were obtained under all models and subgroups. Our meta-analysis showed a significant association between rs4977574 polymorphism and IS risk in allele model (G vs A P = .002, OR = 1.137, 95% CIs 1.048-1.234); with respect to rs2383207 polymorphism, no significant association between that and the risk of IS was detected under the dominant model (GA + AA vs GG, P = .061, OR = 0.923, 95% CIs 0.849-1.004), or recessive model (AA vs GA + GG, P = .656, OR = 0.972, 95% CIs 0.858-1.101), or allele model (A vs G, P = .326, OR = 0.952, 95% CIs 0.863-1.050). Likewise, no significant association between rs2383207 and IS was found in different stoke subtypes (P > .05). CONCLUSIONS: Our findings indicated G allele of lncRNA ANRIL rs4977574 could increase the risk of IS, and the variant may be associated with susceptibility to LAA-IS in Chinese Han population.


Assuntos
Predisposição Genética para Doença/genética , AVC Isquêmico/genética , Polimorfismo Genético/genética , RNA Longo não Codificante/sangue , Idoso , Alelos , Grupo com Ancestrais do Continente Asiático/etnologia , Grupo com Ancestrais do Continente Asiático/genética , Aterosclerose/epidemiologia , Aterosclerose/etnologia , Aterosclerose/genética , Estudos de Casos e Controles , China/epidemiologia , China/etnologia , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etnologia , Doença da Artéria Coronariana/genética , Feminino , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla , Genótipo , Humanos , AVC Isquêmico/epidemiologia , AVC Isquêmico/etnologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco
18.
Medicine (Baltimore) ; 100(11): e25150, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725999

RESUMO

BACKGROUND: The association between cytochrome P450 2C19 (CYP2C19) polymorphisms and neurological deterioration in stroke or transient ischemic attack (TIA) patients is not completely understood. Hence, we performed a systematic review and meta-analysis of prospective cohort studies to quantify this association. METHODS: PubMed, Cochrane Library, Excerpta Medica Database, China National Knowledge Infrastructure and WanFang databases were searched for studies published up to April 2019. Prospective cohort studies that reported an association between CYP2C19 polymorphisms and neurological deterioration in stroke/TIA patients were included. Data on risk ratio (RR) and 95% confidence intervals (CI) were extracted and pooled by the authors. Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines were followed. RESULTS: Twelve eligible studies were included. Twelve studies reported CYP2C19∗2, ∗3 loss-of-function alleles and 5 studies reported CYP2C19∗17 gain-of-function allele. Compared to non-carriers, carriers of CYP2C19∗2, ∗3 loss-of-function alleles had a significantly higher risk of neurological deterioration (RR, 1.63; 95%CI, 1.32-2.02). Conversely, carriers of CYP2C19∗17 gain-of-function allele had a significantly lower risk of neurological deterioration (RR, 0.520; 95%CI, 0.393-0.689) compared to non-carriers. CONCLUSIONS: This meta-analysis demonstrated that the carriers of CYP2C19∗2, ∗3 loss-of-function alleles have an increased risk of neurological deterioration compared to non-carriers in stroke or TIA patients. Additionally, CYP2C19∗17 gain-of-function allele can reduce the risk of neurological deterioration.


Assuntos
Citocromo P-450 CYP2C19/genética , Ataque Isquêmico Transitório/patologia , Degeneração Neural/genética , Polimorfismo Genético/genética , Acidente Vascular Cerebral/patologia , Idoso , Feminino , Humanos , Ataque Isquêmico Transitório/genética , Mutação com Perda de Função/genética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Acidente Vascular Cerebral/genética
19.
Eur Rev Med Pharmacol Sci ; 25(2): 890-897, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33577043

RESUMO

OBJECTIVE: The aim of this study was to explore the associations of interleukin-1ß (IL-1ß) and IL-6 gene polymorphisms with the pathogenesis of Parkinson's disease. PATIENTS AND METHODS: A total of 200 patients with Parkinson's disease in our hospital were collected as the disease group. Meanwhile, 200 healthy subjects were taken as the control group. Peripheral blood samples were drawn from all research subjects. The polymorphic regions of IL-1ß and IL-6 were amplified via polymerase chain reaction (PCR). Moreover, the polymorphisms were detected and analyzed, followed by further analysis based on the changes in gene expressions and Hoehn-Yahr grade of patients. RESULTS: The allele distributions at IL-1ß rs571556428 (p=0.015) and IL-6 rs543214973 (p=0.012) were statistically different between control group and disease group. In disease group, the G allele frequency at IL-1ß rs571556428 and T allele frequency at IL-6 rs543214973 were significantly higher (p<0.05). Genotype distributions at IL-1ß rs572292175 (p=0.017) and rs571556428 (p=0.000), and IL-6 rs543214973 (p=0.002) in disease group were also different from those in control group. In addition, the frequencies of CT genotype at IL-1ß rs572292175, AA genotype at IL-1ß rs571556428 and AA genotype at IL-6 rs543214973 in disease group were significantly lower (p<0.05). After modeling and analysis, it was found that the distribution of recessive model at IL-1ß rs571556428 (p=0.012) and IL-6 rs543214973 (p=0.014) in disease group exhibited significant differences from those in control group. The frequencies of TA haplotype at IL-1ß rs572292175 and rs571556428 (p=0.038) and GA haplotype at IL-6 rs1474348 and rs543214973 (p=0.047) in disease group were lower than those in control group (p<0.05). The polymorphisms at IL-1ß rs571556428 and IL-6 rs1474348 were significantly associated with gene expression (p<0.05). Moreover, the expressions of IL-1ß and IL-6 rose significantly in patients with GG genotype at rs571556428 and CG genotype at rs1474348, respectively (p<0.05). Furthermore, the polymorphism at IL-1ß rs571556428 was significantly correlated with the grade of Parkinson's disease (p=0.000). Parkinson's disease was in a higher grade (grade 4-5) in patients with AA genotype, whereas in a lower grade (grade 1-2) in patients with GG and AG genotypes. CONCLUSIONS: IL-1ß and IL-6 gene polymorphisms are significantly associated with the pathogenesis of Parkinson's disease.


Assuntos
Interleucina-1beta/genética , Interleucina-6/genética , Doença de Parkinson/genética , Polimorfismo Genético/genética , Feminino , Humanos , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico
20.
BMC Public Health ; 21(1): 145, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33530977

RESUMO

BACKGROUND: Evidence for the impact of the food retailing environment on food-related and obesity outcomes remains equivocal, but only a few studies have attempted to identify sub-populations for whom this relationship might be stronger than others. Genetic polymorphisms related to dopamine signalling have been associated with differences in responses to rewards such as food and may be candidate markers to identify such sub-populations. This study sought to investigate whether genetic variation of the dopamine D4 receptor gene (DRD4 exon III 48 bp VNTR polymorphism) moderated the association between local exposure to food retailers on BMI and diet in a sample of 4 to12-year-old children. METHODS: Data collected from a birth cohort and a community cross-sectional study conducted in Montreal, Canada, were combined to provide DRD4 VNTR polymorphism data in terms of presence of the 7-repeat allele (DRD4-7R) for 322 children aged between 4 and 12 (M (SD): 6.8(2.8) y). Outcomes were Body Mass Index (BMI) for age and energy density derived from a Food Frequency Questionnaire. Food environment was expressed as the proportion of local food retailers classified as healthful within 3 km of participants' residence. Linear regression models adjusted for age, sex, income, cohort, and geographic clustering were used to test gene*environment interactions. RESULTS: A significant gene*food environment interaction was found for energy density with results indicating that DRD4-7R carriers had more energy dense diets than non-carriers, with this effect being more pronounced in children living in areas with proportionally more unhealthy food retailers. No evidence of main or interactive effects of DRD4 VNTR and food environment was found for BMI. CONCLUSIONS: Results of the present study suggest that a genetic marker related to dopamine pathways can identify children with potentially greater responsiveness to unhealthy local food environment. Future studies should investigate additional elements of the food environment and test whether results hold across different populations.


Assuntos
Polimorfismo Genético , Receptores de Dopamina D4/genética , Canadá , Criança , Pré-Escolar , Estudos Transversais , Genótipo , Humanos , Repetições Minissatélites , Polimorfismo Genético/genética
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