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1.
Artigo em Inglês | MEDLINE | ID: mdl-32087013

RESUMO

OBJECTIVES: Serum CA72-4 levels are elevated in some gout patients but this has not been comprehensively described. The present study profiled serum CA72-4 expression in gout patients and verified the hypothesis that CA72-4 is a predictor of future flares in a prospective gout cohort. METHODS: To profile CA72-4 expression, a cross-sectional study was conducted in subjects with gouty arthritis, asymptomatic hyperuricaemia, four major arthritis types (OA, RA, SpA, septic arthritis) and healthy controls. A prospective gout cohort study was initiated to test the value of CA72-4 for predicting gout flares. During a 6-month follow-up, gout flares, CA72-4 levels and other gout-related clinical variables were observed at 1, 3 and 6 months. RESULTS: CA72-4 was highly expressed in patients with gouty arthritis [median (interquartile range) 4.55 (1.56, 32.64) U/ml] compared with hyperuricaemia patients [1.47 (0.87, 3.29) U/ml], healthy subjects [1.59 (0.99, 3.39) U/ml] and other arthritis patients [septic arthritis, 1.38 (0.99, 2.66) U/ml; RA, 1.58 (0.95, 3.37) U/ml; SpA, 1.56 (0.98, 2.85) U/ml; OA, 1.54 (0.94, 3.34) U/ml; P < 0.001, respectively]. Gout patients with frequent flares (twice or more in the last year) had higher CA72-4 levels than patients with fewer flares (fewer than twice in the last year). High CA72-4 level (>6.9 U/ml) was the strongest predictor of gout flares (hazard ratio = 3.889). Prophylactic colchicine was effective, especially for patients with high CA72-4 levels (P = 0.014). CONCLUSION: CA72-4 levels were upregulated in gout patients who experienced frequent flares and CA72-4 was a useful biomarker to predict future flares.

2.
Pediatr Nephrol ; 35(3): 441-446, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31811538

RESUMO

BACKGROUND: The prevalence of hyperuricemia is increasing in adults, while the prevalence among adolescents is seldom reported. METHODS: A cross-sectional survey by multistage, stratified sampling method was carried out in Shandong Province during 2017-2018. A total of 9371 adolescents aged from 13 to 19 years were randomly sampled and analyzed in this survey. RESULTS: The overall mean serum uric acid (sUA) concentration was 6.08 ± 1.57 mg/dL and overall hyperuricemia prevalence was 25.4% and 60.5% (when hyperuricemia was defined as sUA ≥ 7 mg/dL or ≥ 5.5 mg/dL). Prevalence were 42.3% (male) and 8.0% (female) when limit was 7 mg/dL and prevalence were 82.1% (male) and 38.4% (female) when limit was 5.5 mg/dL. Male gender, increased body mass index, increased waist circumstance, increased triglycerides, increased fasting blood glucose, increased systolic blood pressure, decreased estimated glomerular filtration rate, and positive family gout history were associated with the enhanced risk of hyperuricemia according to univariate and/or multivariate logistic regression analysis. Food intake frequency of carbonate beverage, mutton, and other kinds varied between hyperuricemia adolescents and normal sUA ones. CONCLUSIONS: The studied adolescent population showed sUA level and hyperuricemia prevalence which are even higher than those of adults in China. The epidemic of youth hyperuricemia may pose a future threat of gout attacks and other hyperuricemia-related diseases, which alarms the public, health professionals and health policy makers to prepare the future health challenges.

3.
Mol Genet Genomic Med ; 7(7): e00722, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31131560

RESUMO

BACKGROUND: To identify potential causative mutations in SLC2A9 and SLC22A12 that lead to hypouricemia or hyperuricemia (HUA). METHODS: Targeted resequencing of whole exon regions of SLC2A9 and SLC22A12 was performed in three cohorts of 31 hypouricemia, 288 HUA and 280 normal controls. RESULTS: A total of 84 high-quality variants were identified in these three cohorts. Eighteen variants were nonsynonymous or in splicing region, and then included in the following association analysis. For common variants, no significant effects on hypouricemia or HUA were identified. For rare variants, six single nucleotide variations (SNVs) p.T21I and p.G13D in SLC2A9, p.W50fs, p.Q382L, p.V547L and p.E458K in SLC22A12, occurred in totally six hypouricemia subjects and were absent in HUA and normal controls. Allelic and genotypic frequency distributions of the six SNVs differed significantly between the hypouricemia and normal controls even after multiple testing correction, and p.G13D in SLC2A9 and p.V547L in SLC22A12 were newly reported. All these mutations had no significant effects on HUA susceptibility, while the gene-based analyses substantiated the significant results on hypouricemia. CONCLUSION: Our study first presents a comprehensive mutation spectrum of hypouricemia in a large Chinese cohort.

4.
Sensors (Basel) ; 19(7)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30939747

RESUMO

The use of renewable energy has increased dramatically over the past couple of decades. Wind farms, consisting of wind turbines, play a vital role in the generation of renewable energy. For monitoring and maintenance purposes, a wind turbine has a variety of sensors to measure the state of the turbine. Sensor measurements are transmitted to a control center, which is located away from the wind farm, for monitoring and maintenance purposes. It is therefore desirable to ensure reliable wireless communication between the wind turbines and the control center while integrating the observations from different sensors. In this paper, we propose an IoT based communication framework for the purpose of reliable communication between wind turbines and control center. The communication framework is based on repeat-accumulate coded communication to enhance reliability. A fusion algorithm is proposed to exploit the observations from multiple sensors while taking into consideration the unpredictable nature of the wireless channel. The numerical results show that the proposed scheme can closely predict the state of a wind turbine. We also show that the proposed scheme significantly outperforms traditional estimation schemes.

5.
Hereditas ; 156: 4, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30679935

RESUMO

Background: Serum uric acid (SUA), hyperuricemia (HUA) and gout are complex traits with relatively high heritability. This study aims to identify whether a candidate gene, SLC28A2, exerts susceptibility for SUA fluctuation and incidence of HUA and gout in the Han Chinese population. Results: Three sample sets of 1376 gout patients, 1290 long-term HUA subjects (no gout attack) and 1349 normouricemic controls were recruited for this study. Eight polymorphisms in the SLC28A2 gene were genotyped using the ligase detection reaction-polymerase chain reaction (LDR-PCR) technology. Rs16941238 showed the most significant associations with SUA level (minor allele "A", BETA = - 13.84 µmol/L, P = 0.0041, Pperm = 0.0042) and HUA (OR = 0.7734, P = 0.0033, Pperm = 0.0020), but not with gout (OR = 0.8801, P = 0.1315, Pperm = 0.1491). Rs2271437 was significantly associated with gout (minor allele "G", OR = 1.387, P = 0.0277, Pperm = 0.0288), and was further confirmed in the meta-analysis with the previously published gout GWAS dataset (OR = 1.3221, P = 0.0089). Each variant basically conferred consistent OR direction on gout and HUA, compared with the normouricemic control. Conclusions: Our findings support the associations of the SLC28A2 gene with the SUA level, the HUA phenotype and gout in Han Chinese.


Assuntos
Gota/genética , Hiperuricemia/genética , Proteínas de Membrana Transportadoras/genética , Ácido Úrico/sangue , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , China , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
6.
Conf Proc IEEE Eng Med Biol Soc ; 2018: 3809-3812, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30441195

RESUMO

Ballistocardiography (BCG) is the measurement of body movement by forces associated with heart contraction that can be used for monitoring cardiac activity. It has already been measured by force sensor and accelerometer. In this research, we developed a capacitive wristband that provides a method for single point, continuous BCG measurement, which has the potential to become a new type of sensor for wearable health care. The aim of this paper is to validate that the signal detected by capacitive electrodes is actually the BCG signal. Signals from four healthy subjects were acquired by a capacitive wristband together with Electrocardiogram (ECG). The capacitive signal was validated by both morphology matching analysis and wave occurrence time matching analysis to show that it is indeed BCG signal. JJ intervals extracted from BCG were shown to have potential to be surrogate of ECG RR series in heart rate variability analysis.


Assuntos
Balistocardiografia , Frequência Cardíaca , Punho , Eletrocardiografia , Eletrodos , Humanos , Processamento de Sinais Assistido por Computador
7.
PLoS One ; 13(1): e0189703, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29351297

RESUMO

In many applications involving epistemic uncertainties usually modeled by belief functions, it is often necessary to approximate general (non-Bayesian) basic belief assignments (BBAs) to subjective probabilities (called Bayesian BBAs). This necessity occurs if one needs to embed the fusion result in a system based on the probabilistic framework and Bayesian inference (e.g. tracking systems), or if one needs to make a decision in the decision making problems. In this paper, we present a new fast combination method, called modified rigid coarsening (MRC), to obtain the final Bayesian BBAs based on hierarchical decomposition (coarsening) of the frame of discernment. Regarding this method, focal elements with probabilities are coarsened efficiently to reduce computational complexity in the process of combination by using disagreement vector and a simple dichotomous approach. In order to prove the practicality of our approach, this new approach is applied to combine users' soft preferences in recommender systems (RSs). Additionally, in order to make a comprehensive performance comparison, the proportional conflict redistribution rule #6 (PCR6) is regarded as a baseline in a range of experiments. According to the results of experiments, MRC is more effective in accuracy of recommendations compared to original Rigid Coarsening (RC) method and comparable in computational time.


Assuntos
Teorema de Bayes , Tomada de Decisões , Modelos Teóricos , Algoritmos
8.
Kidney Int ; 93(1): 69-80, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28729031

RESUMO

The urate oxidase (Uox) gene encodes uricase that in the rodent liver degrades uric acid into allantoin, forming an obstacle for establishing stable mouse models of hyperuricemia. The loss of uricase in humans during primate evolution causes their vulnerability to hyperuricemia. Thus, we generated a Uox-knockout mouse model on a pure C57BL/6J background using the transcription activator-like effector nuclease (TALEN) technique. These Uox-knockout mice spontaneously developed hyperuricemia (over 420 µmol/l) with about 40% survival up to 62 weeks. Renal dysfunction (elevated serum creatinine and blood urea nitrogen) and glomerular/tubular lesions were observed in these Uox-knockout mice. Male Uox-knockout mice developed glycol-metabolic disorders associated with compromised insulin secretion and elevated vulnerability to streptozotocin-induced diabetes, whereas female mice developed hypertension accompanied by aberrant lipo-metabolism. Urate-lowering drugs reduced serum uric acid and improved hyperuricemia-induced disorders. Thus, uricase knockout provides a suitable mouse model to investigate hyperuricemia and associated disorders mimicking the human condition, suggesting that hyperuricemia has a causal role in the development of metabolic disorders and hypertension.


Assuntos
Hiperuricemia/enzimologia , Rim/metabolismo , Fígado/enzimologia , Urato Oxidase/deficiência , Ácido Úrico/sangue , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Pressão Sanguínea , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/enzimologia , Diabetes Mellitus Experimental/genética , Modelos Animais de Doenças , Progressão da Doença , Dislipidemias/sangue , Dislipidemias/enzimologia , Dislipidemias/genética , Feminino , Predisposição Genética para Doença , Supressores da Gota/farmacologia , Hipertensão/enzimologia , Hipertensão/genética , Hipertensão/fisiopatologia , Hiperuricemia/sangue , Hiperuricemia/tratamento farmacológico , Hiperuricemia/genética , Insulina/sangue , Rim/patologia , Rim/fisiopatologia , Lipídeos/sangue , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Fatores de Tempo , Urato Oxidase/genética
9.
Intern Med J ; 47(10): 1147-1153, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28696562

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is associated with the risk of coronary heart diseases; however, the relationship between NAFLD and peripheral artery disease (PAD) in patients with type 2 diabetes has not been investigated. AIM: To investigate the association between NAFLD and PAD in patients with type 2 diabetes. METHODS: We carried out a cross-sectional study on 2646 type 2 diabetes patients ≥ 40 years. All patients provided fasting blood samples and underwent a liver ultrasonography and ankle-brachial index (ABI) test. PAD was defined as an ABI <0.9. Multiple logistic regression analyses were performed to investigate the odds ratio (OR) for PAD associated with NAFLD. RESULTS: Our analyses showed that patients with NAFLD had a significantly higher prevalence of PAD compared with those without NAFLD (12.8% vs 7.8%). NAFLD was associated with a 75% (OR 1.75, 95% confidence interval (CI) 1.35-2.28) increased risk of PAD after adjustment for demographic factors. Addition of various metabolic risk factors as confounders attenuated the association (OR 1.49, 95% CI 1.12-2.00). Further adjustment for C-reactive protein led the association to be marginally significant (OR 1.33, 95% CI 0.99-1.80). Analyses stratified by gender suggested the association was much stronger among women than among men. CONCLUSION: Type 2 diabetes patients with NAFLD had a higher prevalence of PAD, and this association was partly, but not entirely, explained by metabolic risk factors and inflammation.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/epidemiologia , Idoso , Índice Tornozelo-Braço/métodos , Glicemia/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Doença Arterial Periférica/sangue , Fatores de Risco , Inquéritos e Questionários
10.
Sci Rep ; 7(1): 4094, 2017 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-28642574

RESUMO

Gout is a chronic disease resulting from elevated serum urate (SU). Previous genome-wide association studies (GWAS) have identified dozens of susceptibility loci for SU/gout, but few have been conducted for Chinese descent. Here, we try to extensively investigate whether these loci contribute to gout risk in Han Chinese. A total of 2255 variants in linkage disequilibrium (LD) with GWAS identified SU/gout associated variants were analyzed in a Han Chinese cohort of 1255 gout patients and 1848 controls. Cumulative genetic risk score analysis was performed to assess the cumulative effect of multiple "risk" variants on gout incidence. 23 variants (41%) of LD pruned variants set (n = 56) showed nominal association with gout in our sample (p < 0.05). Some of the previously reported gout associated loci (except ALDH16A1), including ABCG2, SLC2A9, GCKR, ALDH2 and CNIH2, were replicated. Cumulative genetic risk score analyses showed that the risk of gout increased for individuals with the growing number (≥8) of the risk alleles on gout associated loci. Most of the gout associated loci identified in previous GWAS were confirmed in an independent Chinese cohort, and the SU associated loci also confer susceptibility to gout. These findings provide important information of the genetic association of gout.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Gota/sangue , Gota/genética , Ácido Úrico/sangue , Alelos , Biomarcadores , China , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Desequilíbrio de Ligação , Masculino , Razão de Chances
11.
Sensors (Basel) ; 17(5)2017 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-28448454

RESUMO

This paper presents a chirp based ultrasonic positioning system (UPS) using orthogonal chirp waveforms. In the proposed method, multiple transmitters can simultaneously transmit chirp signals, as a result, it can efficiently utilize the entire available frequency spectrum. The fundamental idea behind the proposed multiple access scheme is to utilize the oversampling methodology of orthogonal frequency-division multiplexing (OFDM) modulation and orthogonality of the discrete frequency components of a chirp waveform. In addition, the proposed orthogonal chirp waveforms also have all the advantages of a classical chirp waveform. Firstly, the performance of the waveforms is investigated through correlation analysis and then, in an indoor environment, evaluated through simulations and experiments for ultrasonic (US) positioning. For an operational range of approximately 1000 mm, the positioning root-mean-square-errors (RMSEs) &90% error were 4.54 mm and 6.68 mm respectively.

12.
Sci Rep ; 6: 31082, 2016 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-27506295

RESUMO

Chromosome 4q25 has been identified as a genomic region associated with gout. However, the associations of gout with the genes in this region have not yet been confirmed. Here, we performed two-stage analysis to determine whether variations in candidate genes in the 4q25 region are associated with gout in a male Chinese Han population. We first evaluated 96 tag single nucleotide polymorphisms (SNPs) in eight inflammatory/immune pathway- or glucose/lipid metabolism-related genes in the 4q25 region in 480 male gout patients and 480 controls. The SNP rs12504538, located in the elongation of very-long-chain-fatty-acid-like family member 6 gene (Elovl6), was found to be associated with gout susceptibility (Padjusted = 0.00595). In the second stage of analysis, we performed fine mapping analysis of 93 tag SNPs in Elovl6 and in the epidermal growth factor gene (EGF) and its flanking regions in 1017 male patients gout and 1897 healthy male controls. We observed a significant association between the T allele of EGF rs2298999 and gout (odds ratio = 0.77, 95% confidence interval = 0.67-0.88, Padjusted = 6.42 × 10(-3)). These results provide the first evidence for an association between the EGF rs2298999 C/T polymorphism and gout. Our findings should be validated in additional populations.


Assuntos
Acetiltransferases/genética , Grupo com Ancestrais do Continente Asiático , Cromossomos Humanos Par 4/genética , Fator de Crescimento Epidérmico/genética , Gota/genética , Adulto , Idoso , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Risco , Fatores Sexuais
13.
PLoS One ; 11(2): e0148082, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26890073

RESUMO

Interleukin (IL)-17 is a proinflammatory cytokine mainly secreted by activated T helper 17 cells and involved in inflammatory immune responses. This study aimed to investigate the association between IL-17 variants as well as serum IL-17 levels with gout in male Chinese Han individuals. A total of 1,101 male gout patients and 1,239 ethic-matched controls were enrolled. Genetic distributions of three variants (rs2275913 in IL-17A, rs763780 in IL-17F, and rs4819554 in IL-17RA) were detected by real-time polymerase chain reaction using the Taqman probe method. The plasma concentrations of IL-17A and IL-17F were measured in 228 gout patients and 198 controls that came from above samples by an enzyme-linked immunosorbent assay. No significant differences were observed in the genetic distribution of these polymorphisms between cases and controls (rs2275913: χ2 = 0.15, p = 0.928 by genotype, χ2 = 0.14, p = 0.711 by allele; rs763780: χ2 = 2.24, p = 0.326 by genotype, χ2 = 0.26, p = 0.609 by allele; rs4819554: χ2 = 1.79, p = 0.409 by genotype, χ2 = 1.46, p = 0.227 by allele). Levels of serum IL-17A and IL-17F were significantly decreased in gout patients (both p<0.001). However, no difference was observed in acute gout patients between different genotypic carriers of rs2275913 and rs763780 regarding serum IL-17A and IL-17F levels (p>0.05). Although the genetic variants in IL-17 we studied in this research do not appear to be involved in the development of gout in male Chinese Han individuals, the IL-17 cytokine family may participate in gouty inflammation in an undefined way, which requires further validation.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Gota/genética , Interleucina-17/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Biomarcadores , Estudos de Casos e Controles , China , Frequência do Gene , Genótipo , Gota/sangue , Humanos , Interleucina-17/sangue , Masculino , Pessoa de Meia-Idade
14.
Stem Cells Int ; 2016: 1365257, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26783398

RESUMO

Epidemiological studies have identified hyperuricemia as an independent risk factor for cardiovascular disease. However, the mechanism whereby hyperuricemia causes atherosclerosis remains unclear. The objective of the study was to establish a new rat model of hyperuricemia-induced atherosclerosis. Wistar-Kyoto rats were randomly allocated to either a normal diet (ND), high-fat diet (HFD), or high-adenine diet (HAD), followed by sacrifice 4, 8, or 12 weeks later. Serum uric acid and lipid levels were analyzed, pathologic changes in the aorta were observed by hematoxylin and eosin staining, and mRNA expression was evaluated by quantitative real-time polymerase chain reaction. Serum uric acid and TC were significantly increased in the HAD group at 4 weeks compared with the ND group, but there was no significant difference in serum uric acid between the ND and HFD groups. Aorta calcification occurred earlier and was more severe in the HAD group, compared with the HFD group. Proliferating cell nuclear antigen, monocyte chemotactic factor-1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 mRNA levels were increased in the HFD and HAD groups compared with the ND group. This new animal model will be a useful tool for investigating the mechanisms responsible for hyperuricemia-induced atherosclerosis.

15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 32(5): 711-4, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26418998

RESUMO

OBJECTIVE To assess the association of single nucleotide polymorphisms (SNPs) of susceptibility genes of type 2 diabetes mellitus (T2DM) with liability to gout among ethnic Han Chinese males from coastal region of Shandong province. METHODS Seven SNPs within the susceptibility genes of T2DM, including rs10773971(G/C) and rs4766398(G/C) of WNT5B gene, rs10225163(G/C) of JAZF1 gene, rs2069590(T/A) of BDKRB2 gene, rs5745709(G/A) of HGF gene, rs1991914(C/A) of OTOP1 gene and rs2236479(G/A) of COL18A1 gene, were typed with a custom-made Illumina GoldenGate Genotyping assay in 480 male patients with gout and 480 male controls. Potential association was assessed with the chi-square test. RESULTS No significant difference was detected for the 7 selected SNPs in terms of genotypic and allelic frequencies (P > 0.05). When age and body mass index (BMI) were adjusted, the 7 genetic variants still showed no significant association with gout. CONCLUSION The genotypes of the 7 selected SNPs are not associated with gout in ethnic Han Chinese male patients from the coastal region of Shandong province. However, the results need to be replicated in larger sets of patients collected from other regions and populations.


Assuntos
Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Gota/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , China/etnologia , Grupos Étnicos , Humanos , Masculino , Pessoa de Meia-Idade
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 32(4): 538-42, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26252103

RESUMO

OBJECTIVE: To assess the association of cytochrome P450 gene single nucleotide polymorphisms (SNPs) with susceptibility to gout in ethnic Han males from coastal regions of Shandong province. METHODS: Four hundred and eighty male patients with gout and 480 healthy male controls were included. Genotyping was carried out with a custom Illumina GoldenGate Genotyping assay to detect SNP rs2275620 of CYP2C8 gene, SNP rs2070676 of CYP2E1 gene, SNP rs837395 of CYP4B1 gene, and SNP rs194150 of TBXAS1 gene. The association was assessed with chi-square test. RESULTS: No significant difference has been found between the two groups in regard to the genotypic and allelic frequencies of the TT, AT, AA genotypes and A, T alleles of the SNP rs2275620 of the CYP2C8 gene (P=0.88; P=0.97), the CC, CG, GG genotypes and C,G alleles of SNP rs2070676 of the CYP2E1 gene (P=0.24; P=0.09), the TT, AT, AA genotypes and A, T alleles of SNP rs837395 of the CYP4B1 (P=0.88; P=0.97), and TT, AT, AA genotypes and the A,T alleles of SNP rs194150 of TBXAS1 gene (P=0.15; P=0.06). CONCLUSION: This study has identified no association of SNP loci rs2275620(A/T) of CYP2C8, rs2070676(C/G) of CYP2E1, rs837395(A/T) of CYP4B1 and rs194150(A/T) of TBXAS1 with gout in ethnic Han males from coastal regions in Shandong province. However, our result needs to be replicated in larger sets of patients collected from other regions and populations.


Assuntos
Hidrocarboneto de Aril Hidroxilases/genética , Citocromo P-450 CYP2C8/genética , Citocromo P-450 CYP2E1/genética , Gota/enzimologia , Gota/genética , Polimorfismo de Nucleotídeo Único , Tromboxano-A Sintase/genética , Adulto , Grupo com Ancestrais do Continente Asiático/etnologia , Grupo com Ancestrais do Continente Asiático/genética , China/etnologia , Suscetibilidade a Doenças , Feminino , Gota/etnologia , Humanos , Masculino , Pessoa de Meia-Idade
17.
Nat Commun ; 6: 7041, 2015 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-25967671

RESUMO

Gout is one of the most common types of inflammatory arthritis, caused by the deposition of monosodium urate crystals in and around the joints. Previous genome-wide association studies (GWASs) have identified many genetic loci associated with raised serum urate concentrations. However, hyperuricemia alone is not sufficient for the development of gout arthritis. Here we conduct a multistage GWAS in Han Chinese using 4,275 male gout patients and 6,272 normal male controls (1,255 cases and 1,848 controls were genome-wide genotyped), with an additional 1,644 hyperuricemic controls. We discover three new risk loci, 17q23.2 (rs11653176, P=1.36 × 10(-13), BCAS3), 9p24.2 (rs12236871, P=1.48 × 10(-10), RFX3) and 11p15.5 (rs179785, P=1.28 × 10(-8), KCNQ1), which contain inflammatory candidate genes. Our results suggest that these loci are most likely related to the progression from hyperuricemia to inflammatory gout, which will provide new insights into the pathogenesis of gout arthritis.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Gota/genética , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único
18.
Rheumatol Int ; 35(6): 963-71, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25377645

RESUMO

Previous studies have showed that patients with gout showed lower serum 25(OH)D levels. As the specific receptor of vitamin D, VDR plays an important role in regulating immune system by combining with vitamin D. In this study, we investigated whether the functional VDR polymorphisms were associated with susceptibility to gout in Chinese Han male population. A total of 504 patients with gout and 523 gout-free controls were recruited from the Affiliated Hospital of the Medical College, Qingdao University. Genotyping of VDR rs11568820, rs2228570 and rs1544410 was performed by TaqMan allele discrimination assays. An association analysis was carried out using the χ(2) test. A genotype-phenotype analysis was also conducted. Our results showed that polymorphisms of rs11568820 and rs1544410 in VDR were associated with gout in Chinese Han male population. The A allele of both rs11568820 and rs1544410 was associated with the risk of gout [P = 0.012 OR 1.251, 95% CI (1.051-1.490); P = 0.006, OR 1.574, 95% CI (1.139-2.175)]. However, there was no statistic significance between rs2228570 and gout (P = 0.186). Our study suggested that the polymorphisms of VDR may be relevant host susceptibility factors for the development of gout in Chinese Han male population. However, further study should be done in a larger size sample and other ethic to test and verify our result.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Gota/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Adulto , Idoso , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Gota/diagnóstico , Gota/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Fatores de Risco , Fatores Sexuais
19.
Int Immunopharmacol ; 23(1): 205-10, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25218163

RESUMO

Many studies have shown that LPS mainly activates four signal transduction pathways to induce inflammation, namely the p38, ERK1/2, JNK and IKK/NF-κB pathways. Studies have demonstrated that 5'-AMP-induced hypothermia (AIH) exhibits high anti-inflammatory capabilities. In this study, we explore that how AIH inhibits the inflammatory response. Wistar rats were divided into five groups: a control group, an LPS group, a 5'-AMP pre-treatment group, a 5'-AMP post-treatment group and a 5'-AMP group. For each group, plasma and lung were collected from the rats at 6h and 12h after LPS injection. ELISA assays were used to detect plasma levels of CD14, CRP and MCP-1. Inflammatory pathway activation and TLR4 expression were assayed separately by Western blot analysis and immunohistochemistry. Our results showed that rats treated with AIH either before or after an LPS-challenge had a significant decrease in plasma levels of CD14, CRP and TLR4 compared with rats that received LPS only. Western blot analysis showed that AIH inhibited the activation of extracellular signal-regulated kinases (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) and NF-κB in inflammatory rats. Our study concluded that AIH attenuated LPS-induced inflammation mainly by inhibiting activation on the ERK1/2, p38, JNK and NF-κB signaling pathways.


Assuntos
Endotoxemia/imunologia , Hipotermia Induzida , NF-kappa B/metabolismo , Monofosfato de Adenosina/metabolismo , Animais , Proteína C-Reativa/metabolismo , Quimiocina CCL2/sangue , Modelos Animais de Doenças , Endotoxemia/induzido quimicamente , Endotoxemia/terapia , Ativação Enzimática , Humanos , Receptores de Lipopolissacarídeos/sangue , Lipopolissacarídeos/administração & dosagem , Sistema de Sinalização das MAP Quinases , Ratos , Ratos Wistar , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
20.
PLoS One ; 7(12): e51327, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23251501

RESUMO

Our previous studies showed that recombinant high-density lipoprotein (rHDL) rHDL74 exhibited higher anti-inflammatory capabilities compared to wild-type rHDL (rHDLwt), while rHDL228 showed hyper-proinflammation. In this paper, we further investigated the potential mechanisms involved in their different inflammatory functions using two models: endotoxemic mice and the RAW264.7 inflammation model. Our results showed that 24 h after the injection of lipopolysaccharide (LPS), mice treated with rHDL74 had a significant decrease in plasma CRP (P<0.01 vs. rHDLwt; P<0.01 vs. LPS), MCP-1 (P<0.05 vs. rHDLwt; P<0.01 vs. LPS) and CD14 (P<0.01 vs. LPS) compared with the mice treated with rHDLwt or the controls that received LPS only. Similar to our previous study, rHDL228 increased the plasma level of CRP (P<0.05 vs. LPS) and MCP-1 (P<0.01 vs. LPS). Our immunohistochemistry and western blot analysis showed that rHDL74 inhibited the activation of NF-κB in endotoxemic mice and JNK and p38 in the RAW264.7 inflammation model, while rHDL228 exacerbated the activation of NF-κB and ERK. In summary, our data suggest that rHDL74 exhibits higher anti-inflammatory activity by decreasing inflammatory factors and inhibiting the activation of NF-κB, JNK and p38, while rHDL228 appears to be hyper-proinflammation by increasing these inflammatory factors and aggravating the activation of NF-κB and ERK.


Assuntos
Apolipoproteína A-I/metabolismo , Cisteína/genética , Endotoxemia/metabolismo , Lipídeos/química , MAP Quinase Quinase 4/metabolismo , NF-kappa B/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Apolipoproteína A-I/genética , Linhagem Celular , Endotoxemia/enzimologia , Camundongos
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