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1.
Front Genet ; 9: 540, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30555509

RESUMO

To determine the role of A disintegrin and metalloproteinase 10 (ADAM10) in genetic susceptibility to Alzheimer's disease (AD) in a representative Chinese sample, we genotyped 362 AD patients and 370 healthy controls for the rs514049A/C and rs653765C/T polymorphisms in the ADAM10 promoter using the SNaPshot technique. We also examined the potential impact of these polymorphisms on the plasma level of soluble receptor for advanced glycation end products (sRAGE), a decoy receptor whose reduction has been associated with a higher risk of AD. Additionally, a meta-analysis was performed using the present study and the largest GWAS from the International Genomics of Alzheimer's Project (IGAP). No significant differences were found in the distributions of genotypes or alleles between AD patients and control subjects. However, age-at-onset stratification analysis revealed that there were significant differences in the genotypes (P = 0.015) and alleles (P = 0.006) of the rs653765 SNP. Furthermore, patients with the rs653765 CC genotype showed a lower ADAM10 level and a faster cognitive deterioration than those in patients with the CT/TT genotype in late-onset AD (LOAD), and the rs653765 CC polymorphism was able to regulate the production of the ADAM10 substrate sRAGE. In contrast, the rs514049 polymorphism was not statistically associated with AD. In the meta-analysis, we observed that both rs514049 (A allele vs. C allele, P = 0.002) and rs653765 (C allele vs. T allele, P = 0.004) were associated with AD risk. The present study indicated that the rs653765 polymorphism might be associated with the risk and development of LOAD; in particular, the risk genotype, CC, may decrease the expression of ADAM10, influencing the plasma levels of sRAGE, and thus may be correlated with the clinical progression of AD.

2.
CNS Neurosci Ther ; 21(8): 619-25, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26178916

RESUMO

AIMS: Alzheimer's disease (AD) is a multifactor disease that has been reported to have a close association with type 2 diabetes (T2D) where the v-akt murine thymoma viral oncogene homolog 1 (AKT1) plays an important role in the protein synthesis pathways and cell apoptosis processes. Evidence has been shown that AKT1 protein may be related to AD risk among patients with T2D. The aim of this study was to analyze the potential association between single nucleotide polymorphisms of AKT1 promoter and the risk of AD among patients with T2D. METHODS: The association between AKT1 polymorphisms and AD risk in patients with T2D was assessed among 574 consecutive unrelated subjects including 112 AD patients with T2D, 231 patients with AD, and 231 healthy controls in a case-control study. The cognitive function of all subjects was assessed using MMSE. Six single nucleotide polymorphisms with minor allele frequency >0.2 (rs2498786, rs74090038, rs2494750, rs2494751, rs5811155, and rs2494752) in AKT1 promoter were analyzed by polymerase chain reaction (PCR), and the concentration of AKT1 protein in serum was tested using enzyme-linked immunosorbent assay (ELISA). RESULTS: Overall, there was statistically significant difference in AKT1 rs2498786 polymorphism. The CC frequency of AKT1 rs2498786 polymorphism in AD with T2D group and AD control group was significantly higher than that in healthy control group (PAD+T2D vs. health < 0.0001, PAD vs. health < 0.0001). However, the difference was not found between AD with T2D group and AD control group. Compared with healthy control group, the plasma levels of AKT1 protein in AD with T2D group (PAD+T2D vs. health < 0.0001) and AD control group (PAD vs. health = 0.0003) decreased significantly. Among genotypes of AKT1 rs2498786 polymorphism, the AKT1 protein level in GG genotype was significantly higher than that in GC genotype (PGG vs. GC < 0.0001) and CC genotype (PGG vs. CC < 0.0001). CONCLUSION: The study suggests that AKT1 rs2498786 polymorphism in insulin signaling pathway may be associated with AD risk and different genotypes may affects levels of protein expression. However, the polymorphism is not shown to be exclusive in AD patients with T2D.


Assuntos
Doença de Alzheimer/genética , Diabetes Mellitus Tipo 2/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-akt/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/sangue , Doença de Alzheimer/epidemiologia , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Masculino , Proteínas Proto-Oncogênicas c-akt/sangue , Risco
3.
Arch Dermatol Res ; 306(10): 939-44, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25297392

RESUMO

Genome-wide association and large cohort studies have consistently linked several single nucleotide polymorphisms (SNPs) located in the CHRNA5/A3/B4 gene cluster to smoking behaviors and nicotine dependence. Smoking is one of the well-established environmental risk factors for psoriasis and also associated with severity of the disease. Then we conduct the study to examine whether the genetic variations related to smoking behavior located in the CHRNA5/A3/B4 gene cluster also predict the risk of psoriasis vulgaris (PV). The investigations may help explain the mechanisms of the smoking-PV relationship. This is a hospital base case-control study including 634 subjects (329 PV patients and 305 controls), all Chinese Han population. 8 SNPs were selected based on findings from recent studies on smoking and nicotine dependence, all located in the nicotinic acetylcholine receptor subunits CHRNA5/A3/B4 gene cluster. The variants were typed by SNaPshot Multiplex Kit (Applied Biosystems Co., USA). We confirmed that smoking, alcohol consumption and higher body mass index (BMI ≥25) were risk factors for PV. However, none of the selected SNPs was associated with PV risk in the overall analysis and stratification analysis. And we found no association between the selected SNPs in CHRNA5/A3/B4 gene cluster and the clinical features of PV in case-only analysis. This exploratory study does not provide a relationship between these smoking-related SNPs in the CHRNA5/A3/B4 gene cluster and PV in Chinese Han population.


Assuntos
Família Multigênica , Proteínas do Tecido Nervoso/genética , Psoríase/genética , Receptores Nicotínicos/genética , Fumar/genética , Tabagismo/genética , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/etnologia , Grupo com Ancestrais do Continente Asiático/genética , Índice de Massa Corporal , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Psoríase/etnologia , Estudos Retrospectivos , Fatores de Risco , Fumar/efeitos adversos , Fumar/etnologia , Tabagismo/etnologia , Adulto Jovem
4.
Mol Biol Rep ; 41(10): 7015-22, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25052186

RESUMO

Smoking, alcohol consumption and higher body mass index (BMI) are well established risk factors for psoriasis and also associated with the clinical traits of the disease. And the genetic influences on these three risk factors indeed exist. Previously studies have demonstrated these risk factors related genetic variants may also play a role in the development of risk factors-related diseases. Then we performed a hospital-based study in order to evaluate the combined effect of the risk factors and their related polymorphism rs6265 in brain-derived neurotrophic factor (BDNF) gene on psoriasis vulgaris (PV) risk and clinic traits. The case-control study involved 660 subjects including 345 cases and 315 controls in Chinese Han population. The variant of rs6265 was typed by SNaPshot Multiplex Kit (Applied Biosystems Co., USA). We confirmed that higher BMI (≥25), smoking and alcohol consumption were risk factors for PV, and the estimated ORs were 1.63(95 % confidence interval (CI); 1.12-2.37), 2.09(95 % CI; 1.44-3.03) and 1.65(95 % CI; 1.15-2.37) respectively. Genotype and allele distributions did not differ significantly between case and control. However, we found combined effect of rs6265 genotype (GG) and higher BMI (≥25) increased risk of PV (OR = 2.09; 95 % CI, 1.02-4.28; P < 0.05; adjusted OR = 3.19; 95 % CI, 1.37-7.45; P < 0.05) and clinically severity of PV (OR = 2.71; 95 % CI, 1.09-6.72; P < 0.05; adjusted OR = 1.25; 95 % CI, 1.10-1.40; P < 0.05). But none such significant combined effect was observed between others genotype (AA and AG) and other risk factors. In conclusions, the combined effect of BDNF rs6265 genotype (GG) and higher BMI may increases the risk and clinical severity of PV in Chinese Han population.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Meio Ambiente , Polimorfismo Genético , Psoríase/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Feminino , Interação Gene-Ambiente , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Psoríase/diagnóstico , Fatores de Risco , Índice de Gravidade de Doença , Adulto Jovem
5.
Gene ; 544(2): 123-7, 2014 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-24792900

RESUMO

BACKGROUND: Many factors associated with causing psoriasis have been reported, such as the genetic and environmental factors. Smoking is one of the well-established environmental risk factors for psoriasis and also associated with the disease severity. In addition, several studies of psoriasis and psoriatic arthritis have documented gene-environment interactions involving smoking behavior. Although gene polymorphisms on nicotinic acetylcholine receptor subunits CHRNB3-CHRNA6 region gene have been found to correlate with smoking behavior and lung cancer susceptibility in Chinese Han population, the combined effect between the smoking-related genetic variants and smoking behavior on psoriasis vulgaris (PV) has been unreported. OBJECTIVE: To evaluate the combined effect of the smoking-related (rs6474412-C/T) polymorphism on CHRNB3-CHRNA6 region gene and smoking behavior on PV risk and clinic traits in Chinese Han population. METHODS: A hospital-based case-control study including 672 subjects (355 PV cases and 317 controls) was conducted. The variant of rs6474412 was typed by SNaPshot Multiplex Kit (Applied Biosystems Co., USA). RESULTS: The higher body mass index (BMI≥25), smoking behavior and alcohol consumption were risk factors for PV, and the estimated ORs were 1.55 (95% CI, 1.09-2.29), 1.74 (95% CI, 1.22-2.49) and 1.81 (95% CI, 1.25-2.62) respectively. The smoking patients had more severe conditions than non-smokers (OR=1.71, 95% CI, 1.08-2.70, P=0.020). The alleles and genotypes of rs6474412 were not associated with risk of PV, but the combined effect of rs6474412 genotype (TT) and smoking behavior increased severity of PV (OR=5.95; 95% CI, 1.39-25.31; P<0.05; adjusted OR=2.20; 95% CI, 1.55-3.14; P<0.001). CONCLUSIONS: Our results demonstrate that the combined effect of rs6474412-C/T polymorphism in smoking-related CHRNB3-CHRNA6 region gene and smoking behavior may not confer risk to PV, but may have impact on PV severity in Chinese Han population.


Assuntos
Psoríase/genética , Receptores Nicotínicos/genética , Índice de Gravidade de Doença , Fumar/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas/efeitos adversos , Grupo com Ancestrais do Continente Asiático/genética , Índice de Massa Corporal , Estudos de Casos e Controles , China , Progressão da Doença , Exposição Ambiental , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Variação Genética , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Psoríase/etiologia , Fatores de Risco , Fumar/efeitos adversos , Adulto Jovem
6.
J Atheroscler Thromb ; 21(8): 878-93, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24727681

RESUMO

AIM: Stroke is a leading cause of death and disability worldwide. Most ischemic strokes (IS) are caused by atherosclerosis. Recently, the pivotal role of ADAM17 in atherosclerosis has been thoroughly addressed. However, the association between ADAM17 and IS has not yet been thoroughly explored. The present study therefore aimed to investigate the association between disintegrin and metalloproteinase 17 (ADAM17) gene polymorphisms and the risk of ischemic stroke (IS). METHODS: The associations between five ADAM17 promoter polymorphisms and the risk of IS were assessed in 342 patients with IS and 296 age-matched healthy individuals in a case-control study. RESULTS: The allele and genotype frequencies of the ADAM17 polymorphisms (rs11684747, rs11689958, rs12692386, rs55790676 and rs1524668) did not differ significantly between the IS patients and healthy control group subjects. In addition, no significant associations were detected between the ADAM17 haplotypes and IS. The mean intima-media thickness in the IS patients was not associated with the ADAM17 polymorphisms. When the IS patients were stratified according to their OCSP classification, the genotype frequencies of the ADAM17-rs1524668 polymorphism exhibited a significant association with the PACI subtype of IS. Moreover, the ADAM17-rs12692386 A>G polymorphism was found to be associated with a higher ADAM17 mRNA expression. CONCLUSIONS: The SNPs in the ADAM17 promoter region do not appear to be major contributors to the pathogenesis of IS. However, the rs12692386 G ADAM17 allele is correlated with a higher expression of ADAM17 mRNA, which may play a role in increasing inflammation in IS patients. Furthermore, the ADAM17-rs1524668 polymorphism is linked to a higher risk of PACI-type stroke, confirming the role of ADAM17 in the pathophysiology of PACI, with potentially important therapeutic implications.


Assuntos
Proteínas ADAM/genética , Isquemia Encefálica/genética , Doenças das Artérias Carótidas/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Acidente Vascular Cerebral/genética , Proteína ADAM17 , Idoso , Isquemia Encefálica/epidemiologia , Doenças das Artérias Carótidas/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Acidente Vascular Cerebral/epidemiologia
7.
Cell Biochem Funct ; 32(2): 201-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24105880

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effect of artemisinin on the proliferation and apoptosis of rat vascular smooth muscle cells (VSMCs). METHOD: Primary rat VSMCs were treated with various doses of artemisinin. Cell proliferation was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the messenger RNA and protein expressions of proliferating cell nuclear antigen were determined by reverse-transcription polymerase chain reaction and immunohistochemistry. Apoptosis was measured using annexin V and propidium iodide double staining evaluated by flow cytometry. Protein expression of Bax, Bcl2, and cyclin-dependent kinase 4 was determined by Western blot. RESULTS: After 72 h of treatment, artemisinin significantly inhibited VSMC proliferation in a dose-dependent manner. Treatment with 1 mM artemisinin for 72 h significantly reduced the expression of proliferating cell nuclear antigen messenger RNA. On the other hand, the same treatment increased the apoptosis of VSMCs, the activation of caspase-3, the Bax protein expression, and the Bax/Bcl2 ratio. CONCLUSION: The results suggest that artemisinin can effectively inhibit VSMC proliferation and induce VSMC apoptosis.


Assuntos
Antimaláricos/farmacologia , Apoptose/efeitos dos fármacos , Artemisininas/farmacologia , Proliferação de Células/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Animais , Aorta Torácica/citologia , Células Cultivadas , Quinase 4 Dependente de Ciclina/genética , Quinase 4 Dependente de Ciclina/metabolismo , Masculino , Músculo Liso Vascular/citologia , Miócitos de Músculo Liso/citologia , Ratos Wistar , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
8.
Biomed Res Int ; 2013: 760904, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24195079

RESUMO

During growth, C. botulinum is always exposed to different environmental changes, such as temperature increase, nutrient deprivation, and pH change; however, its corresponding global transcriptional profile is uncharacterized. This study is the first description of the genome-wide gene expression profile of C. botulinum in response to heat shock stress. Under heat stress (temperature shift from 37°C to 45°C over a period of 15 min), 176 C. botulinum ATCC 3502 genes were differentially expressed. The response included overexpression of heat shock protein genes (dnaK operon, groESL, hsp20, and htpG) and downregulation of aminoacyl-tRNA synthetase genes (valS, queA, tyrR, and gatAB) and ribosomal and cell division protein genes (ftsZ and ftsH). In parallel, several transcriptional regulators (marR, merR, and ompR families) were induced, suggesting their involvement in reshuffling of the gene expression profile. In addition, many ABC transporters (oligopeptide transport system), energy production and conversion related genes (glpA and hupL), cell wall and membrane biogenesis related genes (fabZ, fabF, and fabG), flagella-associated genes (flhA, flhM, flhJ, flhS, and motAB), and hypothetical genes also showed changed expression patterns, indicating that they may play important roles in survival under high temperatures.


Assuntos
Proteínas de Bactérias/biossíntese , Clostridium botulinum/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Resposta ao Choque Térmico/fisiologia , Viabilidade Microbiana , Proteínas de Bactérias/genética , Clostridium botulinum/genética , Perfilação da Expressão Gênica , Genes Bacterianos/fisiologia , Temperatura Alta
9.
CNS Neurosci Ther ; 19(10): 785-94, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23773531

RESUMO

AIM: Dysregulation of the activity of the disintegrin/metalloproteinase ADAM10 could contribute to the development of atherosclerosis. Although a number of genetic studies have focused on the association of ADAM10 gene polymorphisms with susceptibility to diseases, no genetic association studies of ADAM10 gene variability with atherosclerotic cerebral infarction (ACI) have been conducted. The aim of this study was to analyze the potential association between ADAM10 promoter polymorphisms and ACI. METHODS: The associations between rs653765 and rs514049 polymorphisms of the ADAM10 promoter and the possible risk of ACI were assessed among 347 patients with ACI and 299 matched healthy individuals in a case-control study. RESULTS: Overall, there was a significant difference in the genotypes frequencies of rs653765 (P = 0.04) between the ACI and control subjects. In addition, the rs653765 mutated allele of ADAM10 was significantly associated with increased ADAM10 expression in patients with ACI (P = 0.032). In contrast, the allele frequency of rs514049 was not statistically associated with ACI, and the rs514049 variant A > C did not affect the expression of ADAM10 either. CONCLUSION: Our findings indicate a positive association between the rs653765 polymorphism of ADAM10 and ACI, as well as a negative result for rs514049. In addition, a significant increase in ADAM10 expression was observed in patients with ACI carrying the rs653765 C > T mutation. This new knowledge about ADAM10 might be clinically important and confirm a role for ADAM10 in the pathophysiology of ACI, with potentially important therapeutic implications.


Assuntos
Proteínas ADAM/genética , Secretases da Proteína Precursora do Amiloide/genética , Grupo com Ancestrais do Continente Asiático/genética , Aterosclerose/genética , Infarto Cerebral/genética , Proteínas de Membrana/genética , Regiões Promotoras Genéticas/genética , Proteína ADAM10 , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático/etnologia , Aterosclerose/diagnóstico , Aterosclerose/etnologia , Estudos de Casos e Controles , Infarto Cerebral/diagnóstico , Infarto Cerebral/etnologia , Feminino , Estudos de Associação Genética/métodos , Humanos , Masculino , Pessoa de Meia-Idade
10.
CNS Neurosci Ther ; 19(7): 469-76, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23575378

RESUMO

AIM: Conclusions on the association between polymorphisms in the vascular endothelial growth factor (VEGF) gene promoter and risk of Alzheimer's disease (AD) are ambiguous, and sufficient evaluation of the association is lacking. Therefore, we performed a meta-analysis of observational studies to explore the association between polymorphisms in the VEGF gene promoter and AD risk. METHODS: Bibliographical searches were performed in the MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases without any language limitations. Three investigators independently assessed abstracts for relevant studies and independently reviewed all eligible studies. A meta-analysis was conducted using a fixed- or random-effects model. Odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the strength of association. All statistical analyses were performed using Stata 11.0 software. RESULTS: The meta-analysis of 2787 AD cases and 2841 controls from eight published case-control studies on the -2578C/A polymorphism and 1422 AD cases and 1063 controls from four studies on the -1154G/A polymorphism did not show any significant associations. However, in a subgroup analysis stratified by the presence of APOE є4, associations were observed with APOE ε4 (-) for -2578C/A (A vs. C: OR = 1.22, 95% CI = 1.04-1.43, P = 0.014; A/A vs. C/C: OR = 1.59, 95% CI = 1.11-2.27, P = 0.011 and A/A vs. A/C + C/C: OR = 1.46, 95% CI = 1.08-1.99, P = 0.015) and -1154G/A (A vs. G: OR = 0.74, 95% CI = 0.62-0.89, P = 0.001; A/A vs. G/G: OR = 0.57, 95% CI = 0.37-0.87, P = 0.009; A/G vs. G/G: OR = 0.69, 95% CI = 0.53-0.89, P = 0.004 and A/A + A/G vs. G/G: OR = 0.66, 95% CI = 0.52-0.85, P = 0.001). CONCLUSION: This meta-analysis showed the risk role of the -2578 polymorphism and the protective role of the -1154 polymorphism when the APOE є4 status was negative, suggesting that the two polymorphisms in the VEGF promoter may have opposing effects on AD risk in an APOE є4-independent manner.


Assuntos
Doença de Alzheimer/genética , Fator A de Crescimento do Endotélio Vascular/genética , Doença de Alzheimer/diagnóstico , Apolipoproteínas E/genética , Intervalos de Confiança , Interpretação Estatística de Dados , Humanos , Razão de Chances , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética
11.
CNS Neurosci Ther ; 19(4): 229-34, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23421912

RESUMO

AIM: Alzheimer's disease (AD) is a multifactor disease that has been reported to have a close association with endoplasmic reticulum (ER) stress response. In the response, the regulator factor human X-box-binding protein 1 (XBP1) has been shown to facilitate the refolding and degradation of misfolded proteins, prevent neurotoxicity of amyloid-beta (Aß) and tau, and play an important role in the survival of neurons. The aim in the study was to analyze the potential association between the -116C/G polymorphism of XBP1 and the risk of AD. METHODS: The association between -116C/G polymorphism of XBP1 promoter and possible risk of AD was assessed among 276 patients with AD and 254 matched healthy individuals in a case-control study. RESULTS: Overall, there was a significantly statistical difference in genotype (P = 0.0354) and allele frequencies (P = 0.0150, OR = 1.3642, 95% CI = 1.0618-1.7528) between the AD subjects and control subjects, showing that the -116C/G polymorphism of XBP1 might lead to increased susceptibility for AD in a Chinese Han population. In addition, the -116CG and -116GG genotypes were significantly associated with increased AD risk in female (P = 0.0217) and in subjects with APOE є4 (-) (P = 0.0070) in stratified analyses, and the -116CC genotype was significantly associated with fast cognitive deterioration in the AD patients (P = 0.0270). CONCLUSION: The study supports a role for the -116C/G polymorphism of XBP1 gene in the pathogenesis of AD, and further studies with a larger sample size and detailed data should be performed in other populations.


Assuntos
Doença de Alzheimer/genética , Proteínas de Ligação a DNA/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Fatores de Transcrição/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Estudos de Casos e Controles , Proteínas de Ligação a DNA/fisiologia , Feminino , Marcadores Genéticos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Transcrição de Fator Regulador X , Fatores de Risco , Fatores de Transcrição/fisiologia , Proteína 1 de Ligação a X-Box
12.
Int J Dermatol ; 52(4): 441-5, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23231661

RESUMO

BACKGROUND: Altered hypothalamic-pituitary-adrenal (HPA) axis response involved in the pathogenesis of stress-associated alopecia areata (AA) has been reported. A novel polymorphism -2T>C of the adrenocorticotropin receptor (ACTHR) can result in an insufficient HPA response to stress; therefore, the functional polymorphism may underlie a role in stress-associated AA. OBJECTIVE: To investigate the relationship between psychosocial factors and the risk of developing AA and to detect the association between the -2T>C polymorphism of ACTHR and AA. METHODS: Stressful situations were evaluated using Holmes and Rahe's social readjustment rating scale. The ACTHR -2T>C polymorphism was examined in 263 patients with AA and 241 controls. RESULTS: Significant elevation of psychological stress experienced by some patients with AA compared with controls (Z = 6.628, P < 0.01). The frequency of the ACTHR C allele showed a significant difference between patients with AA and controls (P = 0.004). Allele C is the risk allele with a dominant model as the -2C allele occurred more often in patients with AA (P = 0.001). There were significant differences between patients with AA with a severe stress attack versus patients with AA with no obvious stress (P < 0.001), whereas the genotype frequencies were not correlated with the type, duration of disease, and age at onset. Notably, the C allele carrier was significantly associated with stress risk in both AA and controls (P = 0.002, OR = 1.576, 95% CI: 1.148-2.162; P = 0.042, OR = 1.529, 95% CI: 1.022-2.288). CONCLUSIONS: These findings suggest AA in some patients may be associated with stress. The ACTHR gene -2T>C variant may be one important factor that influences stress perception of patients with AA.


Assuntos
Alopecia em Áreas/genética , Alopecia em Áreas/psicologia , Receptores da Corticotropina/genética , Estresse Psicológico/genética , Adolescente , Adulto , Idoso , Alelos , Alopecia em Áreas/etiologia , Criança , Pré-Escolar , Feminino , Frequência do Gene , Heterozigoto , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Percepção , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Estresse Psicológico/complicações , Adulto Jovem
13.
Ann Nutr Metab ; 60(1): 44-51, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22286863

RESUMO

BACKGROUND: The association between the MTHFR C677T polymorphism and hyperuricemia has been investigated in several studies. Although these epidemiological studies have shown that genetic factors are determinants of serum uric acid levels, the power of the association is weak due to the small sample size. METHODS: To study whether the MTHFR C677T polymorphism has an effect on hyperuricemia, we carried out a meta-analysis of case-control studies from PubMed, EMBASE and CNKI (China National Knowledge Infrastructure) databases mainly in English and Chinese. We used the odds ratio (OR) as main effect size; explored potential sources of heterogeneity; performed subgroup analyses by race and performed sensitivity analyses of studies meeting the Hardy-Weinberg equilibrium (HWE). RESULTS: Six studies with 1,470 subjects were included in the meta-analysis. Tests for heterogeneity showed the difference in OR among studies was not statistically significant (p = 0.63, I(2) = 0). When excluding the study of Caucasians not in HWE, the association remained robust (OR = 1.82, 95% CI 1.52-2.17) in the East Asian subgroup and sensitivity analyses. CONCLUSIONS: Although the mechanism of the relationship between the C677T polymorphism and uric acid still remains unclear, these original articles showed that the MTHFR C677T polymorphism may be an independent risk factor for hyperuricemia.


Assuntos
Hiperuricemia/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Grupo com Ancestrais do Continente Europeu/genética , Extremo Oriente/epidemiologia , Feminino , Predisposição Genética para Doença , Humanos , Hiperuricemia/epidemiologia , Irã (Geográfico)/epidemiologia , Masculino , Razão de Chances
14.
Zhonghua Yi Xue Za Zhi ; 91(26): 1825-9, 2011 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-22093783

RESUMO

OBJECTIVE: To investigate the association of interleukin 8 (IL-8) gene polymorphisms with the risks of inflammatory bowel disease (IBD). METHODS: Single nucleotide polymorphisms (SNPs) of IL-8 gene at -845 T/C, -738 T/A, -353 A/T, -251 T/A and +678 T/C were analyzed in 183 IBD patients. They included Crohn's disease (CD, n = 41), ulcerative colitis (UC, n = 142) and healthy controls (n = 160). The methods of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-sequence specific primers (PCR-SSP) were employed. RESULTS: No association was observed between any of these five SNPs in IL-8 gene with the occurrence of IBD. A specific haplotype AAT (-353 A/T, -251 T/A & +678 T/C) was over-represented in UC cases when compared with controls (31.0% vs 23.7%, P = 0.046). But the distributions of this haplotype did not show significant difference between CD cases and controls. CONCLUSION: Our data support a significant but modest association between the AAT haplotype of IL-8 gene and UC (OR = 1.441, 95%CI 1.007 - 2.063).


Assuntos
Doenças Inflamatórias Intestinais/genética , Interleucina-8/genética , Polimorfismo de Nucleotídeo Único , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/epidemiologia , Genótipo , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Adulto Jovem
15.
Zhonghua Yi Xue Za Zhi ; 91(18): 1250-3, 2011 May 17.
Artigo em Chinês | MEDLINE | ID: mdl-21756796

RESUMO

OBJECTIVE: To investigate whether the macrophage inflammatory protein 1 alpha (MIP-1α) and apolipoprotein E (ApoE) gene polymorphisms, either alone or in combination, affect the susceptibility to inflammatory bowel disease (IBD). METHODS: Genomic DNA of IBD patients with Crohn's disease (CD, n = 41) and with ulcerative colitis (UC, n = 142) and healthy controls (n = 160) was extracted and genotyped for the MIP-1α and ApoE gene polymorphisms by restriction fragment length polymorphism assay. RESULTS: MIP-1α -906(TA)(6)/(TA)(6) homozygotes had a significantly elevated risk of UC (OR = 1.909, 95%CI = 1.204 - 3.028). The carriers of APOE4ε4 were at a significantly higher risk for UC with OR of 2.379 (95% CI = 1.451 - 3.896). And a combination of these two loci, MIP-1α -906(TA)(6)/(TA)(6)/APOE4ε4 were strongly associated with a higher risk of UC (OR = 3.288; 95%CI = 1.777 - 6.084). CONCLUSION: The polymorphisms of MIP-1α -906 (TA)(6)/(TA)(6) and ApoE are probably independent genetic risk factors for UC. And the coexistence of both may exert an additive effect on the UC risks.


Assuntos
Apolipoproteínas E/genética , Quimiocina CCL3/genética , Colite Ulcerativa/genética , Polimorfismo Genético , Polimorfismo de Fragmento de Restrição , Adulto , Estudos de Casos e Controles , Doença de Crohn/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Clin Exp Med ; 10(1): 59-68, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19779959

RESUMO

In recent years, there have been numerous papers emphasizing the relationship between Glutathione S-transferases polymorphisms and bladder cancer risk, but the findings have not reached a consensus. The relationship between glutathione S-transferase T 1 null genotype and bladder cancer susceptibility is now even more disputable. Therefore, we present a meta-analysis of (nested) case-controlled, genotype-based studies (including 37 studies, 6,986 cases and 9,166 controls) examining this association. Using a fixed-effect model, statistically significant increase was observed between glutathione S-transferase T 1 deletion and bladder cancer risk for the overall studies (OR = 1.12; 95% confidence interval (CI): 1.04-1.21; P = 0.004 for Z test; I (2) = 47.43 for heterogeneity). After adjusting the result using trim-and-fill method, the outcome still had significant difference with little downgrade (OR = 1.10, 95% CI = 1.02-1.18). Three potential sources of heterogeneity including ethnicity, source of control and smoking status were also assessed. Minor increased correlation was found only in population-based studies (OR = 1.16; 95% CI = 1.03-1.30; I (2) = 47.16). Our analysis suggests that glutathione S-transferase T 1 null status is associated with a modest increase in the risk of bladder cancer and the difference exiting in source of control has been confirmed. Due to limited sample size, various confounding variables as well as discrepancy in study design, a valid conclusion still cannot be confirmed.


Assuntos
Suscetibilidade a Doenças , Glutationa Transferase/genética , Polimorfismo Genético , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Animais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Deleção de Sequência
17.
World J Gastroenterol ; 15(29): 3676-80, 2009 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-19653348

RESUMO

AIM: To explore the effect of Astragalus mongholicus polysaccharide (APS) on gene expression and mitogen-activated protein kinase (MAPK) transcriptional activity in intestinal epithelial cells (IEC). METHODS: IEC were divided into control group, lipopolysaccharide (LPS) group, LPS+ 50 microg/mL APS group, LPS+ 100 microg/mL APS group, LPS+ 200 microg/mL APS group, and LPS+ 500 microg/mL APS group. Levels of mRNAs in LPS-induced inflammatory factors, tumor necrosis factor (TNF)-alpha and interleukin (IL)-8, were measured by reverse transcription-polymerase chain reaction. MAPK protein level was measured by Western blotting. RESULTS: The levels of TNF-alpha and IL-8 mRNAs were significantly higher in IEC with LPS-induced damage than in control cells. APS significantly abrogated the LPS-induced expression of the TNF-alpha and IL-8 genes. APS did not block the activation of extracellular signal-regulated kinase or c Jun amino-terminal kinase, but inhibited the activation of p38, suggesting that APS inhibits LPS-induced production of TNF-alpha and IL-8 mRNAs, possibly by suppressing the p38 signaling pathway. CONCLUSION: APS-modulated bacterial product-mediated p38 signaling represents an attractive strategy for prevention and treatment of intestinal inflammation.


Assuntos
Astrágalo (Planta)/química , Interleucina-8/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Polissacarídeos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Animais , Linhagem Celular , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Expressão Gênica/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos , Fosforilação/efeitos dos fármacos , Polissacarídeos/isolamento & purificação , Ratos , Fatores de Tempo
18.
Chin Med J (Engl) ; 122(20): 2483-8, 2009 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-20079164

RESUMO

BACKGROUND: The most significant biological change in intervertebral disc degeneration is the decrease of chondrocyte specific gene and protein expression of Sox9 and collagen type II. Interleukin-1 (IL-1) is not expressed in the normal intervertebral disc tissue but increases in the degenerated intervertebral disc tissue. This suggests that IL-1 may play a role in regulation of the expression of Sox9 and collagen type II. METHODS: Human intervertebral disc cells were isolated and cultured. Sox9 and collagen type II expression during treatment with IL-1, with or without the nuclear factor-kappaB (NF-kappaB) activity inhibitor curcumin, were detected by using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, and the activity of the NF-kappaB signaling pathway was detected by the electrophoretic mobility shift assay (EMSA). RESULTS: IL-1 lowered the mRNA level and protein expression of Sox9 and collagen type II in the cultured intervertebral disc cells in a dose dependent manner (P < 0.05), and this effect was attenuated by curcumin. Curcumin alone had no effect on Sox9 and collagen type II expression (P > 0.05). IL-1 at concentrations of 0.1 ng/ml, 1 ng/ml and 10 ng/ml could stimulate the activity of NF-kappaB in the intervertebral disc cells in a dose dependent manner (P < 0.05) that was inhibited by curcumin. CONCLUSIONS: We demonstrated the previously unknown function of IL-1 in inhibiting Sox9 and collagen type II via NF-kappaB in the intervertebral disc cells. This inhibition can be attenuated by curcumin, which is an effective NF-kappaB activity inhibitor.


Assuntos
Colágeno Tipo II/metabolismo , Curcumina/farmacologia , Interleucina-1/farmacologia , Disco Intervertebral/citologia , NF-kappa B/metabolismo , Fatores de Transcrição SOX9/metabolismo , Adulto , Células Cultivadas , Colágeno Tipo II/genética , Ensaio de Desvio de Mobilidade Eletroforética , Expressão Gênica/efeitos dos fármacos , Humanos , Immunoblotting , Masculino , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição SOX9/genética
19.
Zhonghua Yi Xue Za Zhi ; 87(38): 2724-6, 2007 Oct 16.
Artigo em Chinês | MEDLINE | ID: mdl-18167255

RESUMO

OBJECTIVE: To investigate the distribution of beta-adrenoceptors at different sites of heart after myocardial infarction (MI). METHODS: 14 dogs were randomly divided into 2 equal groups: MI group, undergoing ligation of the left anterior descending coronary artery, and control group undergoing sham-operation. Four weeks later metoprolol, a beta 1-adrenergic receptor antagonist, was injected intravenously. Doppler tissue imaging (DTI) was used to evaluate the peak systolic myocardial velocity (Sm) of the regions apical and basal to the infarction region before and after the injection. Then the dogs were killed with their hearts taken out. Reverse-transcriptase polymerase chain reaction was used to examine the mRNA expression of beta 1-receptor and beta 2-receptor in the non-infracted myocardial tissues apical and basal to the infarction region. RESULTS: The Sm values at the regions apical and basal to the infarction region of the MI group were 3.93 +/- 0.47 and 0.81 +/- 0.19 cm/s respectively, both significantly lower than those of the control group (10.84 +/- 1.97 and 5.85 +/- 1.15 cm/s respectively, both P < 0.05). After injection of metoprolol, the Sm values at the regions apical and basal to the infarction region of the MI group were 3.43 +/- 0.37 and 0.73 +/- 0.14 cm/s respectively, not significantly different from those before the injection; however, the corresponding Sm values of the control group were 8.69 +/- 1.14 and 4.33 +/- 0.29 cm/s respectively, both significantly lower than those before the injection (both P < 0.05). The mRNA expression levels of beta 1-receptor decreased in both apical and basal regions in the MI group compared with those in the control group, and the degree of expression decrease at the apical region was significantly greater than that at the basal region. However, there was no significant difference in the expression level of beta 1-receptor mRNA between the apical and basal regions in the control group. There was no significant difference in the mRNA expression of beta 2-receptor in different regions of the heart in both groups. CONCLUSION: After MI regional variation occurs for the beta 1-receptor mRNA expression, but not to the beta 2-receptor.


Assuntos
Infarto do Miocárdio/fisiopatologia , Miocárdio/metabolismo , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genética , Antagonistas de Receptores Adrenérgicos beta 1 , Antagonistas de Receptores Adrenérgicos beta 2 , Antagonistas Adrenérgicos beta/farmacologia , Animais , Doença Crônica , Modelos Animais de Doenças , Cães , Expressão Gênica , Metoprolol/farmacologia , Infarto do Miocárdio/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
Zhonghua Yi Xue Za Zhi ; 86(35): 2495-501, 2006 Sep 19.
Artigo em Chinês | MEDLINE | ID: mdl-17156681

RESUMO

OBJECTIVE: To investigate the characteristic changes of expression of the genes with specific functions in acute spinal cord injury (SCI). METHODS: Nine SD rats were randomly divided into 3 equal groups: SCI 8-hour group in which modified Allen's falling strike method was used to establish spinal cord contusion model, the spinal cords were taken out 8 hours later to undergo examination of the gene expression profile by using cDNA microarray including 13 200 gene, 12 genes were selected to undergo semi-quantitative RT-PCR, and the up-regulation of the candidate gene C/EBPdelta was verified by in situ hybridization and immunohistochemistry.; SCI 72-hour group undergoing the same treatment, however, with the spinal cord taken out 72 hours later; and control group undergoing only sham operation with the spinal cord taken out immediately. RESULTS: In the SCI 8 hour group the expression of 52 genes differed in comparison with the control group, 30 genes, including those related to transcription factors, oxidative stress, complement, pro-inflammatory reaction, and anti-inflammatory reaction, were up-regulated and 22 genes related to ion channel, synaptic proteins, and cytoskeletal proteins, were down-regulated. In the SCI 72-hour group the expression of 44 genes with known functions related to growth/differentiation/survival, axonal guidance, neuron regeneration, signal transduction, ubiquitin-proteasome system, and tumor suppressor differed, 26 genes were up-regulated and 18 down-regulated, in comparison with the control group. Semi-quantitative RT-PCR results of the 12 genes were consistent with those by the microarray examination. CONCLUSION: Significant changes occur in the early stage of SCI. Expressed at a high level in SCI, C/EBPdelta may be a therapeutic target of SCI.


Assuntos
Perfilação da Expressão Gênica , Análise de Sequência com Séries de Oligonucleotídeos , Traumatismos da Medula Espinal/genética , Medula Espinal/metabolismo , Animais , Proteína delta de Ligação ao Facilitador CCAAT/genética , Proteína delta de Ligação ao Facilitador CCAAT/metabolismo , Modelos Animais de Doenças , Imuno-Histoquímica , Hibridização In Situ , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Traumatismos da Medula Espinal/etiologia
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