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2.
Front Immunol ; 12: 626609, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34084161

RESUMO

Accurate detection of anti-SARS-CoV-2 antibodies provides a more accurate estimation of incident cases, epidemic dynamics, and risk of community transmission. We conducted a cross-sectional seroprevalence study specifically targeting different populations to examine the performance of pandemic control in Taiwan: symptomatic patients with epidemiological risk and negative qRT-PCR test (Group P), frontline healthcare workers (Group H), healthy adult citizens (Group C), and participants with prior virologically-confirmed severe acute respiratory syndrome (SARS) infection in 2003 (Group S). The presence of anti-SARS-CoV-2 total and IgG antibodies in all participants were determined by Roche Elecsys® Anti-SARS-CoV-2 test and Abbott SARS-CoV-2 IgG assay, respectively. Sera that showed positive results by the two chemiluminescent immunoassays were further tested by three anti-SARS-CoV-2 lateral flow immunoassays and line immunoassay (MIKROGEN recomLine SARS-CoV-2 IgG). Between June 29 and July 25, 2020, sera of 2,115 participates, including 499 Group P participants, 464 Group H participants, 1,142 Group C participants, and 10 Group S participants, were tested. After excluding six false-positive samples, SARS-CoV-2 seroprevalence were 0.4, 0, and 0% in Groups P, H, and C, respectively. Cross-reactivity with SARS-CoV-2 antibodies was observed in 80.0% of recovered SARS participants. Our study showed that rigorous exclusion of false-positive testing results is imperative for an accurate estimate of seroprevalence in countries with previous SARS outbreak and low COVID-19 prevalence. The overall SARS-CoV-2 seroprevalence was extremely low among populations of different exposure risk of contracting SARS-CoV-2 in Taiwan, supporting the importance of integrated countermeasures in containing the spread of SARS-CoV-2 before effective COVID-19 vaccines available.


Assuntos
Anticorpos Antivirais/sangue , COVID-19/epidemiologia , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/epidemiologia , Adulto , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Reações Cruzadas , Estudos Transversais , Surtos de Doenças , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Síndrome Respiratória Aguda Grave/imunologia , Taiwan/epidemiologia
3.
Cancer Genet ; 256-257: 81-85, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33975123

RESUMO

Low-grade endometrial stromal sarcoma and ossifying fibromyxoid tumors are two types of mesenchymal tumors that share no similarities in terms of site, sex, and morphological characteristics. They are rare, low grade tumors of uncertain lineage, with no definite immunological markers. Interestingly, a common PHF1 gene- related rearrangement was observed in these two tumors. Here, we report a case of endometrial stromal sarcoma with distinct ossification. Microscopically, the tumor is composed of bland-looking ovoid cells with low cellularity in the fibromyxoid stroma. Foci of metaplastic bone formation were noted. Using a combination of FISH, transcriptome sequencing, and molecular techniques, we identified a new PHF1-BRD8 fusion transcript, which was previously described, but in its reciprocal fusion form. This case expands the current understanding of low-grade endometrial stromal sarcoma and emphasizes the importance of molecular characterization of unique fusion, which may be related to its distinct morphological features and the possibly chemosensitive target.


Assuntos
Neoplasias do Endométrio/patologia , Proteínas de Fusão Oncogênica/metabolismo , Osteogênese , Sarcoma/patologia , Sequência de Bases , Neoplasias do Endométrio/genética , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas Proto-Oncogênicas c-mdm2/genética , Sarcoma/genética , Coloração e Rotulagem , Células Estromais/patologia , Transcriptoma/genética
4.
J Microbiol Immunol Infect ; 54(5): 816-829, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33676864

RESUMO

BACKGROUND/PURPOSE: Our study goals were to evaluate the diagnostic performance of four anti-SARS-CoV-2 antibodies tests and the differences in dynamic immune responses between COVID-19 patients with and without pneumonia. METHODS: We collected 184 serum samples from 70 consecutively qRT-PCR-confirmed COVID-19 patients at four participating hospitals from 23 January 2020 to 30 September 2020. COVID-19 pneumonia was defined as the presence of new pulmonary infiltration. Serum samples were grouped by the duration after symptom onset on a weekly basis for antibody testing and analysis. The four immunoassays: Beckman SARS-CoV-2 IgG/IgM (Beckman Test), Siemens (ADVIA Centaur®) SARS-CoV-2 Total (COV2T) (Siemens Test), SBC COVID-19 IgG ELISA (SBC Test) and EliA SARS-CoV-2-Sp1 IgG/IgM/IgA P2 Research (EliA Test) were used for detecting the SARS-CoV-2 specific antibodies. RESULTS: The sensitivity of all tests reached 100% after 42 days of symptom onset. Siemens Test, the only test detecting total anti-SARS-CoV-2 antibodies, had the best performance in the early diagnosis of COVID-19 infection (day 0-7: 77%; day 8-14: 95%) compared to the other 3 serological tests. All tests showed 100% specificity except SBC Test (98%). COVID-19 patients with pneumonia had significantly higher testing signal values than patients without pneumonia (all p values < 0.05, except EliA IgM Test). However, Siemens Test and SBC Test had highest probability in early prediction of the presence of COVID-19 pneumonia. CONCLUSION: Chronological analysis of immune response among COVID-19 patients with different serological tests provides important information in the early diagnosis of SARS-CoV-2 infection and prediction of the risk of pneumonia after infection.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Imunoensaio/métodos , Pneumonia/diagnóstico , SARS-CoV-2/isolamento & purificação , Adulto , Anticorpos Antivirais/sangue , Formação de Anticorpos , Diagnóstico Precoce , Ensaio de Imunoadsorção Enzimática , Reações Falso-Positivas , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Testes Sorológicos , Taiwan
5.
Emerg Microbes Infect ; 9(1): 2157-2168, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32940547

RESUMO

This multicenter, retrospective study included 346 serum samples from 74 patients with coronavirus disease 2019 (COVID-19) and 194 serum samples from non-COVID-19 patients to evaluate the performance of five anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests, i.e. two chemiluminescence immunoassays (CLIAs): Roche Elecsys® Anti-SARS-CoV-2 Test (Roche Test) and Abbott SARS-CoV-2 IgG (Abbott Test), and three lateral flow immunoassays (LFIAs): Wondfo SARS-CoV-2 Antibody Test (Wondfo Test), ASK COVID-19 IgG/IgM Rapid Test (ASK Test), and Dynamiker 2019-nCoV IgG/IgM Rapid Test (Dynamiker Test). We found high diagnostic sensitivities (%, 95% confidence interval [CI]) for the Roche Test (97.4%, 93.4-99.0%), Abbott Test (94.0%, 89.1-96.8%), Wondfo Test (91.4%, 85.8-94.9%), ASK Test (97.4%, 93.4-99.0%), and Dynamiker Test (90.1%, 84.3-94.0%) after >21 days of symptom onset. Meanwhile, the diagnostic specificity was 99.0% (95% CI, 96.3-99.7%) for the Roche Test, 97.9% (95% CI, 94.8-99.2%) for the Abbott Test, and 100.0% (95% CI, 98.1-100.0%) for the three LFIAs. Cross-reactivity was observed in sera containing anti-cytomegalovirus (CMV) IgG/IgM antibodies and autoantibodies. No difference was observed in the time to seroconversion detection of the five serological tests. Specimens from patients with COVID-19 pneumonia demonstrated a shorter seroconversion time and higher chemiluminescent signal than those without pneumonia. Our data suggested that understanding the dynamic antibody response after COVID-19 infection and performance characteristics of different serological test are crucial for the appropriate interpretation of serological test result for the diagnosis and risk assessment of patient with COVID-19 infection.


Assuntos
Anticorpos Antivirais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Imunoensaio/métodos , Medições Luminescentes/métodos , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Adulto , Idoso , Anticorpos Antivirais/sangue , Betacoronavirus/genética , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Feminino , Humanos , Imunoensaio/normas , Medições Luminescentes/normas , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Reprodutibilidade dos Testes , SARS-CoV-2 , Soroconversão , Testes Sorológicos , Índice de Gravidade de Doença , Taiwan/epidemiologia
6.
J Infect ; 81(3): 435-442, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32553841

RESUMO

OBJECTIVES: We aimed to evaluate the role of rapid serological tests in the management of coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study enrolled 16 real-time reverse transcription polymerase chain reaction-confirmed symptomatic patients with COVID-19 and 58 COVID-19 negative patients at a medical center in Taiwan over a 3-month period. Serial serum samples were collected and tested for antibody response using four point-of-care (POC) lateral flow immunoassays (LFIA) (ALLTEST 2019-nCoV IgG/IgM Rapid Test, Dynamiker 2019-nCoV IgG/IgM Rapid Test, ASK COVID-19 IgG/IgM Rapid Test, and Wondfo SARS-CoV-2 Antibody Test). Time-dependent detection sensitivity and timeliness of seroconversion were determined and compared between the four POC rapid tests. RESULTS: The overall sensitivity and specificity of the four tests for detecting anti-SARS-CoV-2 antibodies after 3 weeks of symptom onset were 100% and 100%, respectively. There was no significant difference between the rapid tests used for detection of IgM and IgG separately and those used for detection of combined total antibody (mainly IgM/IgG). There was no significant difference between the four POC rapid tests in terms of time required for determining seroconversion of COVID-19. Patients with COVID-19 with pneumonia demonstrated shorter seroconversion time than those without pneumonia. CONCLUSION: Though the POC antibody rapid tests based on LFIA showed reliable performance in the detection of SARS-CoV-2-specific antibodies, the results of these tests should be interpreted and applied appropriately in the context of antibody dynamic of COVID-19 infection. COVID-19 patients complicated with pneumonia exhibited earlier anti-SARS-CoV-2 antibody response than COVID-19 patients without pneumonia.


Assuntos
Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Imunoensaio/métodos , Pneumonia Viral/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Testes Sorológicos/métodos , Adulto , COVID-19 , Estudos de Casos e Controles , Infecções por Coronavirus/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/imunologia , Estudos Retrospectivos , SARS-CoV-2 , Sensibilidade e Especificidade , Eliminação de Partículas Virais
8.
Am J Nephrol ; 50(6): 454-464, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31639806

RESUMO

BACKGROUND: After angioplasty, veins are more prone to intimal hyperplasia than arteries. Veins tend to produce less nitric oxide (NO), which could lead to endothelial dysfunction. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase and contributes to cardiovascular disease. In humans, dimethylarginine dimethylaminohydrolase 1 (DDAH1) is the major enzyme for ADMA degradation. In this study, we aim to determine whether venous intimal hyperplasia in hemodialysis (HD) vascular access is influenced by common polymorphisms in the DDAH1 genes. METHODS: This is a prospective observational cohort study. A total of 473 HD patients referred for the angioplasty of vascular access were enrolled. There were 190 arteriovenous grafts (AVG) and 283 arteriovenous fistulas (AVF). The follow-up lasted for 2 years after the interventions. Seven single nucleotide polymorphisms (SNPs) in DDAH1 were genotyped and ADMA were measured at baseline. The primary outcome was restenosis after angioplasty. RESULTS: Among the 7 SNPs, plasma ADMA levels were significantly different in DDAH1 rs233112 (GA + GG vs. AA, 0.86 ± 0.23 vs. 0.82 ± 0.19 µM, p = 0.03) and rs1498373 (CT + TT vs. CC, 0.87 ± 0.23 vs. 0.82 ± 0.20 µM, p = 0.02) genotypes. The AVF group with GG + GA genotype of rs233112 and CT + TT genotype of rs1498373 had higher risks of early restenosis at 3 months. In the AVG group, only GG + GA genotype of rs233112 was associated with early restenosis. A combined analysis of AVG and AVF groups showed that patients with rs233112 GA + GG genotype and rs1498373 CT + TT genotype had higher risks of early restenosis (both p < 0.001). The multivariate analysis results showed that the association of these genotypes with early restenosis is independent of clinical, access, or biochemical factors. CONCLUSIONS: Our findings suggest that certain DDAH1 polymorphisms modulate circulating ADMA levels and are associated with venous intimal hyperplasia.


Assuntos
Amidoidrolases/genética , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Oclusão de Enxerto Vascular/genética , Diálise Renal/efeitos adversos , Túnica Íntima/patologia , Veias/patologia , Idoso , Idoso de 80 Anos ou mais , Amidoidrolases/metabolismo , Arginina/análogos & derivados , Arginina/sangue , Arginina/metabolismo , Feminino , Seguimentos , Oclusão de Enxerto Vascular/sangue , Oclusão de Enxerto Vascular/epidemiologia , Oclusão de Enxerto Vascular/patologia , Humanos , Hiperplasia/genética , Hiperplasia/patologia , Hiperplasia/cirurgia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos
9.
Cephalalgia ; 38(3): 466-475, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28952330

RESUMO

Background Susceptibility genes for migraine, despite it being a highly prevalent and disabling neurological disorder, have not been analyzed in Asians by genome-wide association study (GWAS). Methods We conducted a two-stage case-control GWAS to identify susceptibility genes for migraine without aura in Han Chinese residing in Taiwan. In the discovery stage, we genotyped 1005 clinic-based Taiwanese migraine patients and 1053 population-based sex-matched controls using Axiom Genome-Wide CHB Array. In the replication stage, we genotyped 27 single-nucleotide polymorphisms with p < 10-4 in 1120 clinic-based migraine patients and 604 sex-matched normal controls by using Sequenom. Variants at LRP1, TRPM8, and PRDM, which have been replicated in Caucasians, were also genotyped. Results We identified a novel susceptibility locus (rs655484 in DLG2) that reached GWAS significance level for migraine risk in Han Chinese ( p = 1.45 × 10-12, odds ratio [OR] = 2.42), and also another locus (rs3781545in GFRA1) with suggestive significance ( p = 1.27 × 10-7, OR = 1.38). In addition, we observed positive association signals with a similar trend to the associations identified in Caucasian GWASs for rs10166942 in TRPM8 (OR = 1.33, 95% confidence interval [CI] = 1.14-1.54, Ppermutation = 9.99 × 10-5; risk allele: T) and rs1172113 in LRP1 (OR = 1.23, 95% CI = 1.04-1.45, Ppermutation = 2.9 × 10-2; risk allele: T). Conclusion The present study is the first migraine GWAS conducted in Han-Chinese and Asians. The newly identified susceptibility genes have potential implications in migraine pathogenesis. DLG2 is involved in glutamatergic neurotransmission, and GFRA1 encodes GDNF receptors that are abundant in CGRP-containing trigeminal neurons. Furthermore, positive association signals for TRPM8 and LRP1 suggest the possibility for common genetic contributions across ethnicities.


Assuntos
Predisposição Genética para Doença/genética , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Guanilato Quinases/genética , Transtornos de Enxaqueca/genética , Proteínas Supressoras de Tumor/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Taiwan
10.
Sci Total Environ ; 612: 1373-1379, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-28898944

RESUMO

BACKGROUND: Arsenic exposure is a global health concern. Several studies have focused on chronic arsenic exposure in adults; however, limited data are available regarding the potential adverse effects of prenatal exposure on fetuses and neonates. OBJECTIVES: To assess which time point maternal arsenic exposure may influence the fetus during pregnancy and birth outcomes. METHODS: In this study, total arsenic concentrations were analyzed in urine samples collected from 130 women with singleton pregnancies (22-45years old) in Taiwan from March to December of 2010. All fetal biometric measurements in each trimester period and birth outcomes at delivery were obtained. We applied a generalized estimating equation model and multivariate regression models to evaluate the associations between maternal urinary total arsenic (UtAs) exposure during pregnancy, fetal biometric measurements, and neonatal birth outcomes. RESULTS: We observed statistically significant correlations between maternal UtAs levels and the fetal biparietal diameter over all three trimesters (ß=-1.046mm, p<0.05). Multiple regression analyses showed a negative association between maternal UtAs levels and chest circumference in the first trimester (ß=-0.721cm, p<0.05), and second-trimester UtAs exposure was associated with decreases in birth weight (ß=-173.26g, p<0.01), head circumference (ß=-0.611cm, p<0.05), and chest circumference (ß=-0.654cm, p<0.05). Dose-response relationships were also observed for maternal UtAs exposure and birth outcomes. CONCLUSIONS: We identified a negative relationship between maternal UtAs levels during pregnancy, fetal development, and neonatal birth outcomes. These findings should be confirmed in future studies with large sample sizes.


Assuntos
Arsênio/urina , Desenvolvimento Fetal , Exposição Materna/efeitos adversos , Adulto , Peso ao Nascer , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Pessoa de Meia-Idade , Análise Multivariada , Gravidez , Análise de Regressão , Taiwan , Adulto Jovem
11.
Environ Res ; 160: 339-346, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29054088

RESUMO

OBJECTIVE: The aim of this study was to clarify the association between organophosphate pesticides (OPs) and attention-deficit/hyperactivity disorder (ADHD) related to oxidative stress and genetic polymorphisms. METHODS: This case-control study enrolled 93 children with ADHD and 112 control children in north Taiwan. Six dialkyl phosphate (DAP) metabolites of OPs and oxidative stress biomarkers were analyzed. Polymorphisms of the dopamine receptor D4 gene (DRD4) were identified. RESULTS: Children with ADHD had significantly higher dimethylphosphate (DMP, 236.69nmol/g cre. vs. 186.84nmol/g cre., p value = 0.01) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA, 28.95µg/g cre. vs. 16.55µg/g cre., p value<0.01) concentrations than control children. Children who carried DRD4 GA/AA genotypes (rs752306) were less likely than those who carried the DRD4 GG genotype to have ADHD (odds ratio [OR]: 0.45, 95% CI: 0.24-0.84). The estimated value of the AP (attributable proportion due to interaction) was 0.59 (95% CI: 0.13-1.05), indicating that 59% of ADHD cases in DMP-exposed children with the DRD4 GG genotype were due to the gene-environment interaction. After adjustment for other covariates, children who carried the DRD4 GG genotype, had been exposed to high DMP levels (more than the median), and had high HNE-MA levels had a significantly increased risk for developing ADHD (OR = 11.74, 95% CI: 2.12-65.04). CONCLUSION: This study indicated a gene-environment interaction in the risk of ADHD in children. The association between DMP and ADHD in children might relate to the mechanism of lipid peroxidation. Dose-response relationships and the combined effects of OPs, oxidative stress, and genetic polymorphism on ADHD should not be neglected.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/induzido quimicamente , Organofosfatos/toxicidade , Estresse Oxidativo , Praguicidas/toxicidade , Receptores de Dopamina D4/genética , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Humanos , Peroxidação de Lipídeos , Masculino , Polimorfismo de Nucleotídeo Único
12.
Artigo em Inglês | MEDLINE | ID: mdl-27384573

RESUMO

Attention deficit/hyperactivity disorder (ADHD) is one of the most common childhood neurobehavioral conditions. Evidence of the negative effects of sugar-sweetened beverages (SSBs) on mental health has not been convincing, although a few studies have found an association between high SSB levels and attention problems in children. This study aimed to test the hypothesis that SSB consumption is associated with ADHD among children. Doctor-diagnosed ADHD cases (n = 173) and non-ADHD controls (n = 159) between age 4 to 15 were recruited. SSB consumption, socio-demographic and lifestyle characteristics of the children, as well as of their mothers' characteristics during pregnancy, were collected using a questionnaire. Blood lead levels and polymorphisms of two commonly verified dopaminergic-related genes (the D4 dopamine receptor gene DRD4 and the dopamine transporter gene DAT1) were also analyzed. There was a dose-response relationship between SSB consumption and ADHD. After covariates were adjusted, children who consumed SSBs at moderate levels and high levels had 1.36 and 3.69 odds, respectively, of having ADHD, compared with those who did not consume SSBs (p for trend < 0.05). Similar results were obtained when females were excluded. Our findings highlighted the adverse correlation between SSB consumption and ADHD and indicated a dose-response effect even after covariates were adjusted.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Bebidas , Edulcorantes , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/genética , Criança , Pré-Escolar , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Feminino , Humanos , Chumbo/sangue , Masculino , Polimorfismo Genético , Receptores de Dopamina D4/genética , Inquéritos e Questionários
13.
Int J Mol Sci ; 17(6)2016 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-27240348

RESUMO

Hemodialysis (HD) is the most commonly-used renal replacement therapy for patients with end-stage renal disease worldwide. Arterio-venous fistula (AVF) is the vascular access of choice for HD patients with lowest risk of infection and thrombosis. In addition to environmental factors, genetic factors may also contribute to malfunction of AVF. Previous studies have demonstrated the effect of genotype polymorphisms of angiotensin converting enzyme on vascular access malfunction. We conducted a multicenter, cross-sectional study to evaluate the association between genetic polymorphisms of renin-angiotensin-aldosterone system and AVF malfunction. Totally, 577 patients were enrolled. Their mean age was 60 years old and 53% were male. HD patients with AVF malfunction had longer duration of HD (92.5 ± 68.1 vs. 61.2 ± 51.9 months, p < 0.001), lower prevalence of hypertension (44.8% vs. 55.3%, p = 0.025), right-sided (31.8% vs. 18.4%, p = 0.002) and upper arm AVF (26.6% vs. 9.7%, p < 0.001), and higher mean dynamic venous pressure (DVP) (147.8 ± 28.3 vs. 139.8 ± 30.0, p = 0.021). In subgroup analysis of different genders, location of AVF and DVP remained significant clinical risk factors of AVF malfunction in univariate and multivariate binary logistic regression in female HD patients. Among male HD patients, univariate binary logistic regression analysis revealed that right-side AVF and upper arm location are two important clinical risk factors. In addition, two single nucleotide polymorphisms (SNPs), rs275653 (Odds ratio 1.90, p = 0.038) and rs1492099 (Odds ratio 2.29, p = 0.017) of angiotensin II receptor 1 (AGTR1), were associated with increased risk of AVF malfunction. After adjustment for age and other clinical factors, minor allele-containing genotype polymorphisms (AA and CA) of rs1492099 still remained to be a significant risk factor of AVF malfunction (Odds ratio 3.63, p = 0.005). In conclusion, we demonstrated that rs1492099, a SNP of AGTR1 gene, could be a potential genetic risk factor of AVF malfunction in male HD patients.


Assuntos
Fístula Arteriovenosa/genética , Peptidil Dipeptidase A/genética , Polimorfismo de Nucleotídeo Único , Receptor Tipo 1 de Angiotensina/genética , Idoso , Angiotensinogênio/genética , Estudos de Casos e Controles , Estudos Transversais , Feminino , Predisposição Genética para Doença , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Receptor Tipo 2 de Angiotensina/genética , Diálise Renal/métodos , Fatores Sexuais
14.
Hum Mol Genet ; 25(8): 1637-47, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-26908610

RESUMO

Familial exudative vitreoretinopathy (FEVR) belongs to a group of genetically and clinically heterogeneous disorders in retinal vascular development. To date, in approximately 50% of patients with FEVR, pathogenic mutations have been detected in FZD4, LRP5, TSPAN12, NDP and ZNF408. In this study, we identified two heterozygous frameshift mutations in RCBTB1 from three Taiwanese cases through exome sequencing. In patient-derived lymphoblastoid cell lines (LCLs), the protein level of RCBTB1 is approximately half that of unaffected control LCLs, which is indicative of a haploinsufficiency mechanism. By employing transient transfection and reporter assays for the transcriptional activity of ß-catenin, we demonstrated that RCBTB1 participates in the Norrin/FZD4 signaling pathway and that knockdown of RCBTB1 by shRNA significantly reduced nuclear accumulation of ß-catenin under Norrin and Wnt3a treatments. Furthermore, transgenic fli1:EGFP zebrafish with rcbtb1 knockdown exhibited anomalies in intersegmental and intraocular vessels. These results strongly support that reduced RCBTB1 expression may lead to defects in angiogenesis through the Norrin-dependent Wnt pathway, and that RCBTB1 is a putative genetic cause of vitreoretinopathies.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/genética , Haploinsuficiência , Neovascularização Fisiológica , Doenças Retinianas/genética , Telangiectasia Retiniana/genética , Análise de Sequência de DNA/métodos , Linhagem Celular , Exoma , Oftalmopatias Hereditárias , Proteínas do Olho/metabolismo , Vitreorretinopatias Exsudativas Familiares , Feminino , Mutação da Fase de Leitura , Predisposição Genética para Doença , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Humanos , Masculino , Proteínas do Tecido Nervoso/metabolismo , Taiwan , Via de Sinalização Wnt
15.
PLoS One ; 11(2): e0149558, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26890918

RESUMO

OBJECTIVE: Nonylphenol (NP) belongs to the family of endocrine disruptors, and it is widely used in industrial applications and is ubiquitous in daily foods. Animal studies have suggested that NP exposure might promote motor hyperactivity, likely by causing deficits in dopaminergic neurons. However, research assessing NP exposure and epidemiology studies on human populations are limited. The aim of this study was to explore the association between child NP exposure and ADHD while considering particular covariants, such as lead levels and dopamine-related gene variations. METHODS: A case-control study was conducted on patients with clinically diagnosed ADHD; the Swanson, Nolan and Pelham, Fourth Revision (SNAP-IV) questionnaire was used to identify normal controls aged 4-15 years. Participants were examined for urinary NP concentrations, blood lead levels, and select single-nucleotide polymorphisms of two dopamine-related genes (D4 dopamine receptor, DRD4, and dopamine transporter, DAT1). Socio-demographic variables, maternal lifestyle factors during pregnancy and family medical history were obtained using a questionnaire. RESULTS: A total of 97 children with doctor-diagnosed ADHD and 110 normal controls were enrolled. The blood lead levels in both groups were similar (1.57±0.73 vs. 1.73±0.77 µg/dL, p = 0.15). No significant difference in urinary NP concentration was found between the children with ADHD and the control subjects (4.52±3.22 µg/g cr. vs. 4.64±2.95 µg/g cr., p = 0.43). ADHD was significantly more prevalent among males in this study (male to female ratio: 5:1 for the ADHD group and 1.3:1 for the control group, p<0.01). The analysis was repeated after excluding the females, but this had no effect on the association between NP and ADHD. The regression model, including or excluding females, indicated no increased odds of having ADHD in the context of NP exposure after adjusting for covariants. CONCLUSION: This study indicated that NP exposure might not promote ADHD in children, even though children in Taiwan had relatively high levels of NP compared to those reported previously and those in developed nations.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/urina , Fenóis/urina , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Creatinina/metabolismo , Demografia , Dopamina/metabolismo , Exposição Ambiental/análise , Feminino , Variação Genética , Humanos , Chumbo/efeitos adversos , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Taiwan
16.
Ren Fail ; 38(2): 228-37, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26643995

RESUMO

OBJECTIVES: Nitric oxide (NO) is a pivotal vasoactive substance modulating arteriovenous fistula (AVF) patency for hemodialysis (HD). Since genetic background could be the predicting factor of AVF malfunction, we aimed to investigate whether the NO-related genotype polymorphisms determine AVF survival rates. METHODS: This is a retrospective, observational, multi-center study involving eight HD units in Taiwan, enrolled 580 patients initiating maintenance HD via AVFs. Genotype polymorphisms of NO-biosynthesis regulating enzymes (DDAH-1, DDAH-2, eNOS and PRMT1) were compared between HD patients with (n = 161) and without (n = 419) history of AVF malfunction. Subgroup analyses by gender were performed to evaluate the genetic effect in difference sexes. RESULTS: In overall population, statistically significant associations were not found between AVF malfunction and the genetic polymorphisms. In the male subgroup (n = 313), a single nucleotide polymorphism (SNP) of PRMT1, rs10415880 (IVS9-193 A/G), showed a significant association with AVF malfunction. Male patients with AA/AG genotype had inferior AVF outcomes compared to GG genotype, regarding primary patency (70.6% vs. 40.9%, p = 0.001), assisted primary patency (81.0% vs. 58.4%, p < 0.001) and secondary patency (83.7% vs. 63.3%, p < 0.001) at a 5-year observation period. From multivariate Cox regression model, the AA/AG genotypes of PRMT1 were an independent risk factor for AVF malfunction in men (HR: 4.539, 95% CI 2.015-10.223; p < 0.001). However, such associations were not found in women. CONCLUSIONS: rs10415880, the SNP of PRMT1 could be a novel genetic marker associated with AVF malfunction risk in male HD patients. Those with AA and AG genotypes of rs10415880 may predict a poorer long-term patency of AVF.


Assuntos
Derivação Arteriovenosa Cirúrgica/efeitos adversos , Óxido Nítrico/biossíntese , Óxido Nítrico/genética , Polimorfismo Genético , Diálise Renal , Feminino , Genótipo , Humanos , Masculino , Estudos Retrospectivos , Fatores Sexuais , Fatores de Tempo
17.
Cephalalgia ; 36(11): 1028-1037, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26643377

RESUMO

Objective Several genetic variants have been found to increase the risk of restless legs syndrome (RLS). The aim of the present study was to determine if these genetic variants were also associated with the comorbidity of RLS and migraine in patients. Methods Thirteen single-nucleotide polymorphisms (SNPs) at six RLS risk loci ( MEIS1, BTBD9, MAP2K5, PTPRD, TOX3, and an intergenic region on chromosome 2p14) were genotyped in 211 migraine patients with RLS and 781 migraine patients without RLS. Association analyses were performed for the overall cohort, as well as for the subgroups of patients who experienced migraines with and without aura and episodic migraines (EMs) vs. chronic migraines (CMs). In order to verify which genetic markers were potentially related to the incidence of RLS in migraine patients, multivariate regression analyses were also performed. Results Among the six tested loci, only MEIS1 was significantly associated with RLS. The most significant SNP of MEIS1, rs2300478, increased the risk of RLS by 1.42-fold in the overall cohort ( p = 0.0047). In the subgroup analyses, MEIS1 augmented the risk of RLS only in the patients who experienced EMs (odds ratio (OR) = 1.99, p = 0.0004) and not those experiencing CMs. Multivariate regression analyses further showed that rs2300478 in MEIS1 (OR = 1.39, p = 0.018), a CM diagnosis (OR = 1.52, p = 0.022), and depression (OR = 1.86, p = 0.005) were independent predictors of RLS in migraine. Conclusions MEIS1 variants were associated with an increased risk of RLS in migraine patients. It is possible that an imbalance in iron homeostasis and the dopaminergic system may represent a link between RLS incidence and migraines.


Assuntos
Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/genética , Proteína Meis1/genética , Síndrome das Pernas Inquietas/epidemiologia , Síndrome das Pernas Inquietas/genética , Adulto , Distribuição por Idade , Causalidade , Comorbidade , Feminino , Estudos de Associação Genética , Marcadores Genéticos/genética , Humanos , Masculino , Transtornos de Enxaqueca/diagnóstico , Polimorfismo de Nucleotídeo Único/genética , Prevalência , Síndrome das Pernas Inquietas/diagnóstico , Distribuição por Sexo , Taiwan/epidemiologia
18.
Cardiovasc Diabetol ; 13: 156, 2014 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-25467091

RESUMO

BACKGROUND AND AIMS: Elevated plasma asymmetric dimethylarginine (ADMA) levels have been observed in patients with insulin resistance and diabetes, and have been reported to predict adverse cardiovascular events in type 2 diabetic patients. However, the relationship between ADMA and glycemic control in patients with type 2 diabetes remained controversial. METHODS AND RESULTS: We evaluated 270 patients with type 2 diabetes and measured their plasma ADMA and hemoglobin A1c (HbA1c) levels by high performance liquid chromatography. The mean age was 67 ± 12 years. The mean plasma ADMA and HbA1c level were 0.46 ± 0.09 µmol/l and 7.8 ± 1.6%, respectively. There was no significant correlation between plasma ADMA level and HbA1c level (r = -0.09, p = 0.13). During the median follow-up period of 5.7 years (inter-quartile range: 5.0 - 7.3 years), major adverse cardiovascular event (MACE, including cardiovascular death, myocardial infarction and stroke) was observed in 55 patients (20.4%). Multivariate Cox regression analysis revealed that the ADMA tertile was an independent risk factor for MACE (ADMA tertile III versus ADMA tertile I: p = 0.026, HR: 2.31, 95% CI: 1.10 - 4.81). The prognosis predictive power of ADMA disappeared in patients with well glycemic control (HbA1c ≤6.5%), and the ADMA-HbA1c interaction p value was 0.01. CONCLUSIONS: In patients with type 2 diabetes, ADMA might be an independent risk factor for long-term adverse cardiovascular events. However, ADMA was not correlated with serum HbA1c level, and in diabetic patients with HbA1c ≤6.5%, elevated ADMA level was no longer associated with increased risk of long-term prognosis. Our findings suggested that the prognosis predictive value of ADMA in type 2 diabetes might be modified by the glycemic control.


Assuntos
Arginina/análogos & derivados , Glicemia/análise , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hemoglobina A Glicada/metabolismo , Idoso , Idoso de 80 Anos ou mais , Arginina/sangue , Arginina/química , Biomarcadores/sangue , Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco
19.
Am J Nephrol ; 37(2): 110-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23363891

RESUMO

BACKGROUND/AIMS: Contrast-induced nephropathy (CIN) is the third most common cause of hospital-acquired acute renal failure. However, the pathogenesis of CIN remains unclear. This study evaluated the role of anti-inflammatory cytokine interleukin-10 (IL-10) and pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) gene polymorphisms as CIN susceptibility markers after percutaneous coronary intervention (PCI). METHODS: Four IL-10 tag SNPs (rs1554286, rs3021094, rs3790622, rs1800896) and three TNF-α tag SNPs (rs1799964, rs1800630, rs1800629) were analyzed by MALDI-TOF mass spectrometry in 53 CIN patients and 455 control subjects. Serum IL-10 and TNF-α were detected using ELISA. RESULTS: When compared to controls, the CIN patients showed increased frequencies of CC (rs1554286) and AG+GG (rs1800896) genotypes in IL-10 and GA+AA (rs1800629) genotype in TNF-α (OR = 2.24 (1.13-4.44), p = 0.018; OR = 2.61 (1.30-5.26), p = 0.005, and OR = 2.11 (1.08-4.09), p = 0.025, respectively). Baseline serum IL-10 levels in CIN patients were significantly lower (1.02 ± 1.14 vs. 2.78 ± 4.73 pg/ml, p = 0.008). Patients with CIN had a higher rate of decline in renal function than those without CIN (0.89 ± 1.67 vs. 0.30 ± 0.95 ml/min/1.73 m(2) per month, p = 0.002). Significantly higher rates of decline in creatinine clearance were noted in patients with TNF-α (rs1800629) GA+AA than GG genotype (0.88 ± 1.83 vs. 0.36 ± 0.70, p = 0.03), and with IL-10 (rs1800896) AG+GG than AA genotype (1.28 ± 2.14 vs. 0.33 ± 0.90, p < 0.001). CONCLUSIONS: Gene polymorphisms of IL-10 and TNF-α are associated with CIN risk and long-term renal outcome after PCI. More prospective studies are needed to confirm our results.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Meios de Contraste/efeitos adversos , Interleucina-10/genética , Fator de Necrose Tumoral alfa/genética , Injúria Renal Aguda/sangue , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Biomarcadores , Estudos de Casos e Controles , Intervalos de Confiança , Creatinina/sangue , Feminino , Frequência do Gene , Humanos , Interleucina-10/sangue , Masculino , Pessoa de Meia-Idade , Razão de Chances , Intervenção Coronária Percutânea/efeitos adversos , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fator de Necrose Tumoral alfa/sangue
20.
Nephrol Dial Transplant ; 28(5): 1284-93, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23345623

RESUMO

BACKGROUND: The objective of this study was to evaluate the interaction between the length polymorphism of the guanosine thymidine repeat [(GT)n] in the heme oxygenase-1 (HO-1) gene and far-infrared (FIR) therapy on access flow (Qa) and arteriovenous fistula (AVF) patency in hemodialysis (HD) patients. METHODS: A total of 280 HD patients were randomized into a control group (n = 141) and the FIR group (n = 139) who received 40 min of FIR therapy three times weekly for a year during the study period from May 2005 to December 2007. Access flow was measured during HD. The [(GT)n] was determined with the definition of long (L) allele as [(GT)n] ≥ 30 and short (S) allele as [(GT)n] < 30. RESULTS: The Qa decreased from S/S to S/L and further to the L/L group but increased by FIR therapy with the highest Qa increase in the S/S group. The incidence of AVF malfunction decreased both from the L/L, S/L to S/S group (32.4 versus 17.2 versus 10.9%, P = 0.007) and from the control group to FIR group (27.5 versus 12.6%, P = 0.004). Significant associations were found between AVF malfunction and the following factors (hazard ratio, P-value): a past history of AVF malfunction (2.45, P = 0.044), FIR therapy (0.369, P = 0.03) and L/L genotypes of HO-1 (2.531 versus S/S + S/L genotypes). The 1-year unassisted patency decreased from 91.9 and 77.6% in S/S and S/L subgroups with and without FIR therapy to 75.8 and 60% for L/L subgroup with and without FIR therapy, respectively (P < 0.001). CONCLUSIONS: FIR therapy improves Qa and patency of AVF in HD patients, with the best protective effect in those with S/S genotype of HO-1.


Assuntos
Fístula Arteriovenosa/terapia , Derivação Arteriovenosa Cirúrgica , Heme Oxigenase-1/genética , Raios Infravermelhos , Falência Renal Crônica/complicações , Polimorfismo Genético/genética , Diálise Renal , Alelos , Fístula Arteriovenosa/etiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Genótipo , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas/genética , Taxa de Sobrevida , Sequências de Repetição em Tandem/genética , Grau de Desobstrução Vascular/genética
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