RESUMO
The A1298C polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene has been reported to be associated with hepatocellular carcinoma (HCC), but there are conflicting results from previous studies. The present study aimed to investigate the association between this polymorphism and the risk of HCC using a meta-analysis of the published studies. Published literature from PubMed and Embase databases was systematically searched to identify relevant studies before October 2014. The Begg test was used to measure publication bias. Sensitivity analyses were performed to ensure the authenticity of the outcome. The meta-analysis results showed significant association between the MTHFR A1298C polymorphism and HCC risk (CC vs AA: OR = 0.52, 95%CI = 0.33-0.81; CC vs AC: OR = 0.50, 95%CI = 0.32-0.79; dominant model: OR = 1.94, 95%CI = 1.24-3.02; recessive model: OR = 1.00, 95%CI = 0.84-1.18). In the subgroup analysis, significant associations between the MTHFR A1298C polymorphism and HCC risk were found in Asians (CC vs AA: OR = 0.46, 95%CI = 0.27-0.78; CC vs AC: OR = 0.41, 95%CI = 0.24-0.71; dominant model: OR = 2.27, 95%CI = 1.33-3.86; recessive model: OR = 1.03, 95%CI = 0.86-1.24). Our results suggest that the MTHFR A1298C polymorphism might be related to increased risk of HCC in Asians. Further large and well-designed studies are needed to confirm these conclusions.
Assuntos
Alelos , Carcinoma Hepatocelular/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias Hepáticas/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo de Nucleotídeo Único , Carcinoma Hepatocelular/epidemiologia , Estudos de Casos e Controles , Humanos , Neoplasias Hepáticas/epidemiologia , Razão de Chances , Viés de Publicação , RiscoRESUMO
Previous studies suggested that dopamine receptors may be associated with drug dependence and impulsive behavior. In this study, we examined whether dopamine receptor D1 (DRD1) is associated with heroin dependence and the impulsive behavior in patients with heroin dependence. The participants included 367 patients with heroin dependence and 372 healthy controls from a Chinese Han population. We examined the potential association between heroin dependence and 8 single-nucleotide polymorphisms (rs686, rs4867798, rs1799914, rs4532, rs5326, rs265981, rs10078714, rs10078866) of DRD1, and the associations between single single-nucleotide polymorphism, haplotypes, and impulsive behavior. Compared with the healthy controls, heroin dependence patients showed a significantly lower frequency of GG homozygotes of rs5326 (P = 0.027), significantly lower frequency of the G allele of rs5326 (P = 0.007, odds ratio = 0.718, 95% confidence interval = 0.565-0.913), and higher frequency of the rs265981 G allele (P = 0.0002, odds ratio = 1.711, 95% confidence interval = 1.281-2.287). Furthermore, strong linkage disequilibrium was observed in 2 blocks (D' > 0.9). However, no association was observed between haplotypes and heroin dependence in the 2 blocks. This genetic behavior correlation study showed that the 2 single-nucleotide polymorphisms, rs5326 and rs265981, were not associated with the impulsive behavior in patients with heroin dependence. These findings indicate that DRD1 gene polymorphisms are related to heroin dependence in a Chinese Han population and may be informative for future genetic or biological studies on heroin dependence.
Assuntos
Dependência de Heroína/genética , Polimorfismo de Nucleotídeo Único , Receptores de Dopamina D1/genética , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , Estudos de Associação Genética , Genótipo , Haplótipos , Humanos , Comportamento Impulsivo , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Razão de ChancesRESUMO
A colored phenotype is an important feature of ornamental fish. In mammals, microphthalmia-associated transcription factor (MITF) was found to regulate the development of melanocytes. In this study, the mitfa cDNA was first cloned from the Japanese ornamental (Koi) carp (Cyprinus carpio L.), an important ornamental freshwater fish. The full-length cDNA of the mitfa gene contains 1634 bp, coding for 412 amino acids in Koi. The identity degree of mitfa amino acid sequences between the Koi carp and zebrafish is 92.9%. We tested the expression of the mitfa gene in several varieties of Koi using reverse transcription-polymerase chain reaction and found that the mitfa gene is highly expressed in the skin tissues of the Taisho sanke and the Procypris merus. Interestingly, the mitfa gene was also expressed in the Kohaku and Yamabaki ogon, although melanocytes were not observed in the skin. Koi carp embryos were transparent and colorless, while after hatching, different types of pigment cells successively emerged in a fixed order. In Taisho sanke, melanocytes first appeared in the trunk at approximately 12 days of age. Subsequently, there was a large area of melanocytes by 30 days of age. The expression level of the mitfa mRNA was low in early embryos and newly hatched larvae, and increased to high levels in 30-day-old fry. The results show that the mitfa gene is involved in regulating fish body color in the development of both melanocytes and pigment cells.
Assuntos
Carpas/genética , Proteínas de Peixes/genética , Melanócitos/metabolismo , Fator de Transcrição Associado à Microftalmia/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Blástula/metabolismo , Carpas/embriologia , Carpas/crescimento & desenvolvimento , Clonagem Molecular , Cor , DNA Complementar/química , DNA Complementar/genética , Regulação da Expressão Gênica no Desenvolvimento , Larva/genética , Fator de Transcrição Associado à Microftalmia/classificação , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Pele/embriologia , Pele/crescimento & desenvolvimento , Pele/metabolismo , Pigmentação da Pele/genéticaRESUMO
Heroin dependence is a debilitating psychiatric disorder with a complex inheritance mechanism. Genetic polymorphisms in functional regions of the glutamate receptor, N-methyl D-aspartate 2A (GRIN2A) gene, which encodes the 2A subunit of the N-methyl D-aspartate (NMDA) receptor, may modulate the risk of heroin addiction. We investigated the potential association between 8 single nucleotide polymorphisms (SNPs) of the GRIN2A gene (SNPs rs3219790, rs1014531, rs8044472, rs8045712, rs9933624, rs9940680, rs1420040, and rs767749) and heroin addiction using the MassARRAY system and GeneScan. A total of 405 heroin-addicted patients and 397 healthy control subjects were recruited for this study. Statistically significant differences were observed for rs3219790 in the promoter region of the GRIN2A gene. The frequency of the (GT)26 repeats in the heroin addiction group was significantly higher than that in the control group [X(2) = 5.475, P = 0.019, odds ratio (OR) = 1.367, 95% confidence interval (CI) = 1.051-1.776]. Strong linkage disequilibrium was observed in block 1 (D' > 0.9). However, significant evidence of linkage disequilibrium was not observed between the 7 SNPs in our sample population. These data suggest that GRIN2A gene polymorphisms confer susceptibility to heroin addiction and support the hypothesis that dysfunction of GRIN2A is involved in the pathophysiological process of heroin addiction.
Assuntos
Dependência de Heroína/genética , Polimorfismo de Nucleotídeo Único , Receptores de N-Metil-D-Aspartato/genética , Adulto , Estudos de Casos e Controles , Humanos , Desequilíbrio de Ligação , Regiões Promotoras GenéticasRESUMO
The aim of this study was to determine whether monocyte/macrophage ß2-AR could act as the therapeutic target of antisympathetic excitation-induced atherosclerotic progression. Cultivated human THP-1 cells were divided into different groups and incubated with isoprenaline, metoprolol, propranolol or ß2-AR blocker for 24 h, together with oxidized low-density lipoprotein (ox-LDL). Afterwards, each group was analyzed for C-C chemokine receptor type 2 (CCR2) expression, monocyte chemotactic protein 1 (MCP-1) release into medium and cell migration ability. In the isoprenaline group, CCR2 protein level was increased, as well as the secretion of MCP-1, and cell motility was enhanced, in a concentration-dependent manner. Propranolol and ICI 118,551 significantly reversed the stimulatory effect of isoprenaline on THP-1 cells induced by ox-LDL, but only high concentrations of metoprolol interfered significantly with the action of isoprenaline (P < 0.05). Isoprenaline or a ß-AR blocker could mediate through ß2-AR, affecting MCP-1 secretion, CCR2 protein expression and cell migration capacity of THP-1 cells. Therefore, monocyte-macrophage ß2-AR may act as a target of antisympathetic excitation-induced atherosclerotic progression.
Assuntos
Antagonistas de Receptores Adrenérgicos beta 2/farmacologia , Aterosclerose/etiologia , Aterosclerose/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Simpatolíticos/farmacologia , Antagonistas de Receptores Adrenérgicos beta 1/farmacologia , Aterosclerose/patologia , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL2/metabolismo , Progressão da Doença , Humanos , Receptores CCR2/metabolismoRESUMO
Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.
Assuntos
Animais , Masculino , Cardiomegalia/genética , Regulação para Baixo/genética , MicroRNAs/metabolismo , Miócitos Cardíacos/patologia , Transdução de Sinais/genética , Regulação para Cima/genética , Algoritmos , Aorta/cirurgia , Biomarcadores , Biologia Computacional , Constrição Patológica/genética , Modelos Animais de Doenças , Prognóstico , Ratos Sprague-DawleyRESUMO
Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.
Assuntos
Cardiomegalia/genética , Regulação para Baixo/genética , MicroRNAs/metabolismo , Miócitos Cardíacos/patologia , Transdução de Sinais/genética , Regulação para Cima/genética , Algoritmos , Animais , Aorta/cirurgia , Biomarcadores , Biologia Computacional , Constrição Patológica/genética , Modelos Animais de Doenças , Masculino , Prognóstico , Ratos Sprague-DawleyRESUMO
This study aimed to investigate the properties of mutations of the active efflux pump genes acrA/B and tolC in Escherichia coli CVCC 1547 when induced by different drugs. The mutations were isolated in vitro by exposing E. coli CVCC 1547 to stepwise increases in the concentration of ceftriaxone (CRO), amikacin (AMK), or ciprofloxacin. The results showed that the minimum inhibitory concentrations for the corresponding drugs increased, as did the minimum inhibitory concentrations for other fluoroquinolones and ß-lactam drugs that were not inducers. DNA sequence analyses of the acrA/B and tolC genes of the mutants and comparison with the parent strain revealed that genetic variations had occurred. Three point mutations resulted in amino acid changes in the proteins expressed. Specifically, strain CRO10 had a mutation in acrA, A309G, that resulted in a Thr-103 to Ala substitution, and a mutation in tolC, G735A, that changed Ala-245 to Thr; strain AMK20 (and AMK30) had a Val-447 to Ile amino acid change in acrB. In addition to the missense mutations in these strains, we detected 7, 20, and 15 nonsense mutations in acrA, acrB, and tolC, respectively. To sum up, multiple genetic sequence variations and some changes in amino acid sequences were detected when E. coli CVCC 1547 was challenged in vitro with CRO, AMK, or ciprofloxacin. These changes may have given rise to multidrug-resistant strains.
Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Farmacorresistência Bacteriana Múltipla/genética , Proteínas de Escherichia coli/genética , Lipoproteínas/genética , Proteínas de Membrana Transportadoras/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Amicacina/farmacologia , Ceftriaxona/farmacologia , Ciprofloxacina/farmacologia , Códon sem Sentido/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica , Mutação de Sentido Incorreto/efeitos dos fármacos , Análise de Sequência de DNARESUMO
Extended-spectrum ß-lactamases (ESBLs) and AmpC ß-lactamases produced by a clinical isolate of Klebsiella pneumoniae from chickens were detected with confirmatory phenotypic tests of the Clinical and Laboratory Standards Institute. The minimum inhibitory concentrations of 18 antibacterial drugs against K. pneumoniae were determined by the 2-fold microdilution method. The genotype and subtype of the ESBL-producing and AmpC ß-lactamase-producing K. pneumoniae isolate were identified by PCR amplification of the enzyme-encoding genes followed by DNA sequencing analysis. K. pneumoniae K(1) isolate was an ESBL-producing and AmpC ß-lactamase-producing bacteria with high resistance to ß-lactam antibiotics, such as penicillins, third-generation cephalosporins, fluoroquinolones, and aminoglycosides. The sequence analysis showed that K. pneumoniae K(1) harbored TEM-type, SHV-type, CTX-M-type, and ACT-type AmpC ß-lactamase nucleotide sequences. The TEM-type sequence was designated as TEM-1; the SHV-type sequence was designated as SHV-11; the CTX-M-type sequence was designated as CTX-M-14. Compared with the ACT-like sequence (EF078894), the ACT-type sequence was characterized by 8 nucleotide mutations (A(75)G, C(84)G, T(90)C, A(105)G, G(213)A, G(246)A, C(309)T, and T(315)C). Only one mutation at position 75 led to an amino acid substitution (Asn28Lys). The bla(ACT) type was an ACT-like derivative.
Assuntos
Proteínas de Bactérias/genética , Galinhas/microbiologia , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/isolamento & purificação , Plasmídeos/genética , beta-Lactamases/genética , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/biossíntese , China , Genes Bacterianos/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Fenótipo , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , beta-Lactamases/biossínteseRESUMO
Circular extrachromosomal elements were observed in a variety of Leishmania species. We show here that two lines originating from the same isolate have been found to contain a circular DNA molecule of 26.6 kb and a linear chromosome of about 250 kb, respectively, which share a homology of more than 20 kb. The circular DNA molecule and its related region on the linear chromosome were cloned and their restriction maps compared. This investigation reveals information about chromosome rearrangement in L. mexicana M379. Further examination will enable us to understand the nature of chromosome rearrangement such as circularization or linearization.