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1.
Artigo em Inglês | MEDLINE | ID: mdl-34619053

RESUMO

Background: To date, the clinical management of advanced hepatocellular carcinoma (HCC) patients remains tough and the mechanisms of E2F transcription factor 1 (E2F1) underlying HCC are obscure. Materials and Methods: Our study integrated datasets mined from several public databases to comprehensively understand the deregulated expression status of E2F1. Tissue microarrays and immunohistochemistry staining was used to validate E2F1 expression level. The prognostic value of E2F1 was assessed. In-depth subgroup analyses were implemented to compare the differentially expressed levels of E2F1 in HCC patients with various tumor stages. Functional enrichments were used to address the predominant targets of E2F1 and shedding light on their potential roles in HCC. Results: We confirmed the elevated expression of E2F1 in HCC. Subgroup analyses indicated that elevated E2F1 level was independent of various stages in HCC. E2F1 possessed moderate discriminatory capability in differentiating HCC patients from non-HCC controls. Elevated E2F1 correlated with Asian race, tumor classification, neoplasm histologic grade, eastern cancer oncology group, and plasma AFP levels. Furthermore, high E2F1 correlated with poor survival condition and pooled HR signified E2F1 as a risk factor for HCC. Enrichment analysis of differentially expressed genes, coexpressed genes, and putative targets of E2F1 emphasized the importance of cell cycle pathway, where CCNE1 and CCNA2 served as hub genes. Conclusions: We confirmed the upregulation of E2F1 and explored the prognostic value of E2F1 in HCC patients. Two putative targeted genes (CCNE1 and CCNA2) of E2F1 were identified for their potential roles in regulating cell cycle and promote antiapoptotic activity in HCC patients.

2.
J Int Med Res ; 48(9): 300060520953234, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32961078

RESUMO

OBJECTIVES: This study aimed to investigate hub genes and their prognostic value in colon cancer via bioinformatics analysis. METHODS: Differentially expressed genes (DEGs) of expression profiles (GSE33113, GSE20916, and GSE37364) obtained from Gene Expression Omnibus (GEO) were identified using the GEO2R tool and Venn diagram software. Function and pathway enrichment analyses were performed, and a protein-protein interaction (PPI) network was constructed. Hub genes were verified based on The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) databases. RESULTS: We identified 207 DEGs, 62 upregulated and 145 downregulated genes, enriched in Gene Ontology terms "organic anion transport," "extracellular matrix," and "receptor ligand activity", and in the Kyoto Encyclopedia of Genes and Genomes pathway "cytokine-cytokine receptor interaction." The PPI network was constructed and nine hub genes were selected by survival analysis and expression validation. We verified these genes in the TCGA database and selected three potential predictors (ZG16, TIMP1, and BGN) that met the independent predictive criteria. TIMP1 and BGN were upregulated in patients with a high cancer risk, whereas ZG16 was downregulated. The immunostaining results from HPA supported these findings. CONCLUSION: This study indicates that these hub genes may be promising prognostic indicators or therapeutic targets for colon cancer.


Assuntos
Neoplasias do Colo , Biologia Computacional , Neoplasias do Colo/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos
3.
IET Syst Biol ; 14(6): 314-322, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33399095

RESUMO

Basing on alternative splicing events (ASEs) databases, the authors herein aim to explore potential prognostic biomarkers for cervical squamous cell carcinoma (CESC). mRNA expression profiles and relevant clinical data of 223 patients with CESC were obtained from The Cancer Genome Atlas (TCGA). Correlated genes, ASEs and percent-splice-in (PSI) were downloaded from SpliceSeq, respectively. The PSI values of survival-associated alternative splicing events (SASEs) were used to construct the basis of a prognostic index (PI). A protein-protein interaction (PPI) network of genes related to SASEs was generated by STRING and analysed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Consequently, 41,776 ASEs were discovered in 19,724 genes, 2596 of which linked with 3669 SASEs. The PPI network of SASEs related genes revealed that TP53 and UBA52 were core genes. The low-risk group had a longer survival period than high-risk counterparts, both groups being defined according to PI constructed upon the top 20 splicing events or PI on the overall splicing events. The AUC value of ROC reached up to 0.88, demonstrating the prognostic potential of PI in CESC. These findings suggested that ASEs involve in the pathogenesis of CESC and may serve as promising prognostic biomarkers for this female malignancy.


Assuntos
Processamento Alternativo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/genética , Biomarcadores Tumorais/genética , Feminino , Redes Reguladoras de Genes , Humanos , Prognóstico
4.
Mol Med Rep ; 20(6): 5002-5020, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638221

RESUMO

MicroRNAs (miRNAs/miRs) have been reported to be closely associated with numerous human diseases, including cholangiocarcinoma (CCA). However, the number of miRNAs known to be involved in CCA is limited, and the association between miR­132­3p and CCA remains unknown. In the present study, the clinical role of miR­132­3p and its potential signaling pathways were investigated by multiple approaches. Reverse transcription­quantitative PCR (RT­qPCR), CCA­associated Gene Expression Omnibus (GEO), ArrayExpress and Sequence Read Archive (SRA) miRNA­microarray or miRNA­sequencing data were screened, and meta­analyses were conducted, in order to calculate the receiver operating characteristic (ROC) curve and standardized mean difference (SMD). The predicted target genes of miR­132­3p were obtained from 12 online databases and were combined with the downregulated differentially expressed genes identified in the RNA­sequencing data of CCA. Gene Ontology annotation and pathway analysis were performed in WebGestalt. Protein­protein interaction analyses were conducted in STRING. The Cancer Genome Atlas (TCGA) mRNA expression profiles were used to validate the expression levels of hub genes at the mRNA level. The Human Protein Atlas was used to identify the protein expression levels of hub genes in CCA tissues and non­tumor biliary epithelium. The meta­analyses comprised 10 groups of RT­qPCR data, eight GEO microarray datasets and one TCGA miRNA­sequencing dataset. The SMD of miR­132­3p in CCA was 0.75 (95% CI: 0.25, 1.24), which indicated that miR­132­3p was overexpressed in CCA tissues. This finding was supported by a summary ROC value of 0.80 (95% CI: 0.76, 0.83). The pooled sensitivity and specificity were 0.81 (95% CI: 0.59, 0.93) and 0.71 (95% CI: 0.58, 0.81), respectively. The relative expression level of miR­132­3p in the early stage of CCA (stages I­II) was 6.8754±0.5279, which was markedly lower than that in the advanced stage (stages III­IVB), 7.3034±0.3267 (P=0.003). Consistently, the miR­132­3p level in low­grade CCA (grades G1­G2) was 6.7581±0.5297, whereas it was 7.1191±0.4651 in patients with high­grade CCA (grades G3­G4) (P=0.037). Furthermore, 555 potential target genes of miR­132­3p in CCA were mainly enriched in the 'Focal Adhesion­PI3K­Akt­mTOR­signaling pathway'. In conclusion, upregulation of miR­132­3p may serve a pivotal role in the tumorigenesis and progression of CCA by targeting different pathways. Further in vitro and in vivo studies are required to support the current findings.


Assuntos
Neoplasias dos Ductos Biliares/genética , Colangiocarcinoma/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Adulto , Idoso , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Genômica , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência de RNA , Transcriptoma , Regulação para Cima
5.
Oncol Lett ; 18(5): 4677-4690, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31611977

RESUMO

Cholangiocarcinoma (CCA) is a type of malignant tumor that originates in the mucosal epithelial cells of the biliary system. It is a highly aggressive cancer that progresses rapidly, has low surgical resection rates and a high recurrence. At present, no prognostic molecular biomarker for CCA has been identified. However, CCA progression is affected by mRNA precursors that modify gene expression levels and protein structures through alternative splicing (AS) events, which create molecular indicators that may potentially be used to predict CCA outcomes. The present study aimed to construct a model to predict CCA prognosis based on AS events. Using prognostic data available from The Cancer Genome Atlas, including the percent spliced index of AS events obtained from TCGASpliceSeq in 32 CCA cases, univariate and multivariate Cox regression analyses were performed to assess the associations between AS events and the overall survival (OS) rates of patients with CCA. Additional multivariate Cox regression analyses were used to identify AS events that were significantly associated with prognosis, which were used to construct a prediction model with a prognostic index (PI). A receiver operating characteristic (ROC) curve was used to determine the predictive value of the PI, and Pearson's correlation analysis was used to determine the association between OS-related AS events and splicing factors. A total of 38,804 AS events were identified in 9,673 CCA genes, among which univariate Cox regression analysis identified 1,639 AS events associated with OS (P<0.05); multivariate Cox regression analysis narrowed this list to 23 CCA AS events (P<0.001). The final PI model was constructed to predict the survival of patients with CCA; the ROC curve demonstrated that it had a high predictive power for CCA prognosis, with a highest area under the curve of 0.986. Correlations between 23 OS-related AS events and splicing factors were also noted, and may thus, these AS events may be used to improve predictions of OS. In conclusion, AS events exhibited potential for predicting the prognosis of patients with CCA, and thus, the effects of AS events in CCA required further examination.

6.
IET Syst Biol ; 13(5): 225-233, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31538956

RESUMO

Altered miRNA expression participates in the biological progress of thyroid carcinoma and functions as a diagnostic marker or therapeutic agent. However, the role of miR-7-2-3p is currently unclear. The authors' study was the first investigation of miR-7-2-3p expression level and diagnostic ability in several public databases. Potential target genes were obtained from DIANA Tools, and function enrichment analysis was then performed. Furthermore, the authors examined expression levels of potential targets in the Human Protein Atlas (HPA) and the Cancer Genome Atlas (TCGA). Finally, the potential transcription factors (TFs) were predicted by JASPAR. TCGA, GSE62054, GSE73182, GSE40807, and GSE55780 revealed that miR-7-2-3p expression in papillary thyroid carcinoma (PTC) tissues was notably lower compared with non-tumour tissues, while its expression in E-MATB-736 showed no remarkable difference. Function enrichment analysis showed that 698 genes were enriched in pathways, including pathways in cancer, and glioma. CCND1, GSK3B, and ITGAV of pathways in cancer were inverse correlations with miR-7-2-3p in both post-transcription and protein levels. According to the TF prediction, the prospective upstream TFs of miR-7-2-3p were ISX, SPI1, PRRX1, and BARX1. MiR-7-2-3p was significantly down-regulated and may act on PTC progression by crucial pathways. However, the mechanisms of miR-7-2-3p need further investigation.


Assuntos
Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Câncer Papilífero da Tireoide/genética , Linhagem Celular Tumoral , Progressão da Doença , Genômica , Humanos , Curva ROC , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/metabolismo , Câncer Papilífero da Tireoide/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
7.
Int J Oncol ; 55(2): 425-438, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31268164

RESUMO

Alternative splicing in tumor cells may be used as a molecular marker for the differential diagnosis of certain tumor types and assessment of prognosis. The aim of the present study was to investigate the associations among alternative splicing events, splicing factors, and the survival of patients with hepatocellular carcinoma (HCC). The alternative splicing event profiles of 371 patients with HCC were downloaded from The Cancer Genome Atlas (TCGA) SpliceSeq data, and the percent­splice­in value for each splicing event was calculated. The association between alternative splicing events and overall survival was evaluated. The most significant prognosis­related splicing events were used to build up a prognostic index (PI). A total of 3,082 survival­associated alternative splicing events were detected in HCC. The final PI based on all of the most significant candidate alternative splicing events exhibited better performance in distinguishing good or poor survival in patients compared to the PI based on a single type of splicing event. Receiver operating characteristic curves confirmed the high efficiency of the PI in predicting the survival of HCC patients, with an area under the curve of 0.914. The overexpression of 32 prognosis­related splicing factor genes could also predict poor prognosis in patients with HCC. In conclusion, the constructed computational prognostic model based on HCC­specific alternative splicing events may be used as a molecular marker for the prognosis of HCC.


Assuntos
Processamento Alternativo , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/secundário , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , RNA Mensageiro/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Curva ROC , Taxa de Sobrevida
8.
Pathol Res Pract ; 215(7): 152424, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31103408

RESUMO

BACKGROUND AND AIM: Extensive research has revealed that microRNAs (miRNAs) play a principle role in cancer, and miRNAs associated with specific cancers have also been identified. The role of microRNA (miR)-302b-5p, which is one of the miRNAs reported in association with cancer, in hepatocellular carcinoma (HCC) is still unclear. Thus, the present study aimed to reveal the expression and potential molecule mechanism of miR-302b-5p in HCC. METHODS: An extensive meta-analysis of data from real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR), Gene Expression Omnibus and ArrayExpress microarrays was used to determine the expression of miR-302b-5p in HCC tissue samples and non-cancerous liver tissue samples. The sensitivity and specificity of miR-302b-5p as an indicator of HCC was estimated by plotting the receiver operating characteristic (ROC) and summarized ROC (sROC). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were employed to unravel the molecular mechanisms and biological functions of miR-302b-5p in HCC. Further, the putative target genes of miR-302b-5p were harvested based on the predicted genes and differentially expressed genes in HCC. Finally, the protein-protein interaction (PPI) network was built to determine the hub genes. RESULTS: According to the RT-qPCR results, the expression of miR-302b-5p was pronouncedly decreased in 39 HCC tissue samples as compared to 39 non-cancerous liver tissue samples. The standard mean difference (SMD) values of all the samples used in the meta-analysis also indicated lower miR-302b-5p expression in the 558 HCC tissue samples than in the 286 non-cancerous liver tissue samples. ROC and sROC analyses showed that miR-302b-5p had good specificity and sensitivity for distinguishing HCC tissue from non-cancerous liver tissue. Bioinformatics analyses identified 227 putative genes, and these genes were evidently enriched in the processes of organelle fission, chromosome and chromatin binding and were centralized in a "lysosome" pathway. The PPI network indicated that DNA topoisomerase II alpha (TOP2 A) was the most prominent hub gene of miR-302b-5p in HCC. Interestingly, according to the TCGA and Genotype-Tissue Expression databases, the mRNA and protein expression of TOP2 A were both elevated in HCC tissue samples as compared to non-cancerous liver tissue samples, and the overall survival and disease-free survival revealed that a high level of TOP2 A might reflect poor HCC outcome. CONCLUSIONS: Our findings indicate that miR-302b-5p might suppress HCC progression, and TOP2 A might be a potential target of miR-302b-5p in HCC. However, in-depth in vivo and in vitro experiments are required to verify these findings and explore the mechanisms involved.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Fígado/metabolismo , MicroRNAs/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Simulação por Computador , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Fígado/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética
9.
J Transl Med ; 17(1): 25, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30642348

RESUMO

BACKGROUND: The present study attempted to identify potential key genes and miRNAs of dyslipidemia in obese, and to investigate the possible mechanisms associated with them. METHODS: The microarray data of GSE66676 were downloaded, including 67 obese samples from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network (WGCNA) analysis was performed using WGCNA package and grey60 module was considered as the highest correlation. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for this module were performed by clusterProfiler and DOSE package. A protein-protein interaction (PPI) network was established using Cytoscape software, and significant modules were analyzed using molecular complex detection. RESULTS: Collagen type I alpha 1 chain gene (COL1A1) had the best significant meaning. After bioinformatic analysis, we identified four miRNAs (hsa-miR-3659, hsa-miR-4658, hsa-miR151a-5p and hsa-miR-151b) which can bind SNPs in 3'UTR in COL1A1. After validation with RT-qPCR, only two miRNAs (hsa-miR-3659 and hsa-miR151a-5p) had statistical significance. CONCLUSIONS: The area of 0.806 for miR-3659 and 0.769 for miR-151a-5p under the ROC curve (AUC) may have good diagnostic value for dyslipidemia. Circulating miR-3659 may be a potential biomarker of dyslipidemia in patients with obesity.


Assuntos
MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Dislipidemias/sangue , Dislipidemias/genética , Obesidade/sangue , Obesidade/genética , Regiões 3' não Traduzidas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sequência de Bases , Biomarcadores/sangue , Análise por Conglomerados , Colágeno Tipo I/genética , Dislipidemias/complicações , Feminino , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Obesidade/complicações , Polimorfismo de Nucleotídeo Único/genética , Mapas de Interação de Proteínas/genética , Curva ROC , Adulto Jovem
10.
Int J Clin Exp Pathol ; 12(4): 1439-1456, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933962

RESUMO

BACKGROUND: The miR-191-5p expression has been reported to increase in hepatocellular carcinoma (HCC), but its clinical value and exact role remain to be further clarified. Thus, a comprehensive analysis was performed in the current study to explore the underlying function of miR-191-5p in HCC. METHODS: HCC-related expression data were collected to conduct a thorough analysis to determine the miR-191-5p expression and its clinical significance in HCC, including microarray data from the Gene Expression Omnibus and ArrayExpress database as well as quantitative real-time polymerase chain reaction (qRT-PCR) data of 178 matched clinical samples. The underlying relationship between miR-191-5p and HCC was also explored on the basis of a series of bioinformatics analyses. RESULTS: The overall pooled meta-analysis showed an overexpression of miR-191-5p in the HCC samples (SMD=0.400, 95% CI=0.139-0.663, P=0.003), consistent with the detected result of the clinical HCC samples through the qRT-PCR analysis. Higher miR-191-5p levels were correlated with advanced TNM stages (III and IV), higher pathological grades, and metastasis. Functionally, 64 potential target genes were acquired for further mechanism analysis. Two pathways (p75 neurotrophin receptor and liver kinase B1-mediated signaling pathways), which were likely modulated by miR-191-5p, were regarded to be linked to the deterioration of HCC. Early growth response 1 and UBE2D3 were identified as the most likely targets for miR-191-5p in HCC and were commonly implied in the top enriched pathways and protein-protein network. CONCLUSIONS: In summary, miR-191-5p may function as a tumor promoter miRNA of HCC, and the miR-191-5p inhibitor may contribute to the targeted HCC treatment in the future.

12.
Cell Physiol Biochem ; 48(3): 1151-1163, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30045016

RESUMO

BACKGROUND/AIMS: The present study attempted to identify the potential key genes and pathways of hyperlipidemia, and to investigate the possible mechanisms associated with them. METHODS: The array data of GSE3059 were downloaded, including thirteen samples of hyperlipidemia from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network analysis (WGCNA) was performed with WGCNA package, and the salmon and midnight blue modules were found as the highest correlation. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for these two modules were performed by cluster Profiler and DOSE package. A protein-protein interaction (PPI) network was established using Cytoscape software, and significant modules were analyzed using Molecular Complex Detection. RESULTS: Five genes (histone deacetylase 4, HDAC4; F2R like trypsin receptor 1, F2RL1; abhydrolase domain containing 2, ABHD2; transmembrane 4 L six family member 1, TM4SF1; and family with sequence similarity 13-member A, FAM13A) were found with a significant meaning. When their expression levels were validated with RT-qPCR, the relative expression levels were lower (HDAC4) and higher (F2RL1, ABHD2, TM4SF1 and FAM13A) in hyperlipidemia than in normal controls (P < 0.05-0.01). Subgroup analysis showed that the relative expression levels of HDAC4 were lower, whereas those of F2RL1 and ABHD2 were higher in Maonan than in Han ethnic groups (P < 0.05). CONCLUSION: Except for genetic factors and environmental exposures, epigenetic influence was another mechanism of hyperlipidemia in our study populations, which needed to further confirm.


Assuntos
Redes Reguladoras de Genes , Hiperlipidemias/genética , Mapas de Interação de Proteínas , Adulto , Idoso , Bases de Dados Genéticas , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Hiperlipidemias/metabolismo , Masculino , Pessoa de Meia-Idade , Regulação para Cima
13.
Lipids Health Dis ; 17(1): 105, 2018 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-29747660

RESUMO

BACKGROUND: Maonan nationality belongs to a mountain ethnic minority in China. Little is known about the association of apolipoprotein A1 gene (APOA1) rs964184 single nucleotide polymorphism (SNP) and serum lipid levels in this population. The aim of this study was to detect the association of the APOA1 rs964184 SNP and several environmental factors with serum lipid profiles in the Chinese Maonan and Han populations. METHODS: Genotypes of the APOA1 rs964184 SNP in 867 individuals of Maonan nationality and 820 participants of Han nationality were determined by polymerase chain reaction and restriction fragment length polymorphism, combined with gel electrophoresis, and confirmed by direct sequencing. RESULTS: The frequencies of CC, CG and GG genotypes of the APOA1 rs964184 SNP were 68.86, 29.18 and 1.96% in the Maonan population, and 63.78, 30.85 and 5.37% in the Han population (P < 0.001). The frequency of the G allele was 16.55% in Maonan and 20.79% in Han (P < 0.001). The G allele carriers had lower high-density lipoprotein cholesterol (HDL-C) levels in Maonan and higher triglyceride (TG) levels in Han peoples than the G allele non-carriers. Subgroup analyses showed that the G allele carriers had lower HDL-C levels in both Maonan males and females; and lower apolipoprotein (Apo) A1 levels and the ApoA1/ApoB ratio in Han males than the G allele non-carriers. Serum lipid parameters in the two ethnic groups were also associated with several environmental factors. CONCLUSIONS: The present study reveals that there may be a racial/ethnic- and/or gender-specific association between the APOA1 rs964184 SNP and serum lipid parameters in our study populations. TRIAL REGISTRATION: Retrospectively registered.


Assuntos
Apolipoproteína A-I/genética , Dislipidemias/genética , Metabolismo dos Lipídeos/genética , Lipídeos/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , China/epidemiologia , HDL-Colesterol/sangue , Dislipidemias/sangue , Dislipidemias/patologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Triglicerídeos/sangue
14.
Sci Rep ; 8(1): 6189, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29670124

RESUMO

Little is known about the association of the BCL3-PVRL2-TOMM40 SNPs and dyslipidemia. This study was to detect 12 BCL3-PVRL2-TOMM40 SNPs, gene-gene and gene-environment interactions on dyslipidemia in the Chinese Maonan population. Genotyping was performed in 1130 normal and 832 dyslipidemia participants. Generalized multifactor dimensionality reduction was used to screen the best interaction combination among SNPs and environmental exposures. Allele and genotype frequencies of the detected SNPs were different between the two groups (P < 0.05-0.001). Association of the 12 SNPs and serum lipid levels was observed (P < 0.004-0.001). Multiple-locus linkage disequilibrium was not statistically independent in the population (D' = 0.01-0.98). The dominant model of rs8100239 and rs157580 SNPs, several haplotypes and G × G interaction haplotypes contributed to a protection, whereas the dominant model of rs10402271, rs3810143, rs519113, rs6859 SNPs, another haplotypes and G × G interaction haplotypes revealed an increased morbidity function (P < 0.05-0.001). There were significant three-locus model involving SNP-SNP, SNP-environment, haplotype-haplotype interactions (P < 0.05-0.001). The subjects carrying several genotypes and haplotypes decreased dyslipidemia risk, whereas the subjects carrying other genotypes and haplotypes increased dyslipidemia risk. The BCL3-PVRL2-TOMM40 SNPs, gene-gene and gene-environment interactions on dyslipidemia were observed in the Chinese Maonan population.


Assuntos
Dislipidemias/etiologia , Epistasia Genética , Interação Gene-Ambiente , Proteínas de Membrana Transportadoras/genética , Nectinas/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição/genética , Alelos , Proteína 3 do Linfoma de Células B , Biomarcadores , China , Dislipidemias/metabolismo , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Estilo de Vida , Desequilíbrio de Ligação , Lipídeos/sangue , Masculino
15.
Arch Gerontol Geriatr ; 76: 202-209, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29554514

RESUMO

OBJECTIVES: To look at the possible effect of IGF2R rs9456497 on cardiovascular risks in a long-lived population. METHODS: IGF-2R rs9456497 was genotyped by iMLDR for 496 long-lived Zhuang Chinese (90-107 y/o) and their offspring (n = 723, 60-75 y/o) and healthy controls (n = 611, 60-75 y/o). Association analyses were then conducted among genotypes and cardiovascular risks. RESULTS: The G genotype (GA/GG) was found to represent more frequently in males of general population. No significantly difference was detected among genotypes in each group except that G genotype tended to reduce the systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels in longevity group. However, after sex stratification, total cholesterol (TC) of each genotype in offspring males was elevated versus relevant genotype in longevity and control group; the triglyceride (TG), fasting plasma glucose (FPG) and BMI of each genotype in longevity group were lower while SBP and DBP were higher than that of the relevant genotype in offspring and controls. After stratified by lipid status, the frequency of G allele was markedly increased in the dyslipidemic subgroup in the combined population and controls. Linear regressive analyses showed that HDL was positively correlated to rs9456497 GA genotype while BMI was negatively correlated to AA genotype in offspring group, whereas TC and TG were reversely while BMI was positively associated with AA genotype in CG. CONCLUSIONS: IGF-2R rs9456497 G genotype correlates to detrimental cardiovascular risks in ordinary population which might partially interpret their less preservation of health as compared to long-lived cohort.


Assuntos
Doenças Cardiovasculares/etiologia , Receptor IGF Tipo 2/genética , Idoso , Idoso de 80 Anos ou mais , Pressão Sanguínea , Doenças Cardiovasculares/genética , Feminino , Genótipo , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco
16.
Int J Clin Exp Pathol ; 11(3): 1466-1483, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31938245

RESUMO

The correlation between the BDNF rs11030104 single nucleotide polymorphism (SNP) and serum lipid levels has been understudied. The present study was conducted to detect the association of the BDNF rs11030104 SNP and several environmental factors with serum lipid levels in the Jing and Han nationalities. Genotypes of the BDNF rs11030104 SNP in 709 unrelated subjects of Han and 706 unrelated participants of Jing populations were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and further verified by direct sequencing. There was no significant difference in either genotypic or allelic frequencies between the Han and Jing populations. The genotypic and allelic frequencies of the SNP in Jing but not in Han populations were different between male and female subgroups (P<0.05 for each). The levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in the Jing population were different among the genotypes, the G allele carriers had lower TC and LDL-C levels than the G allele non-carriers. Subgroup analyses showed that the differences in serum TC and LDL-C levels among the genotypes were observed in the Jing males but not in females. Serum lipid profiles were also significantly associated with some environmental factors in the Han and Jing populations, or in male and female subgroups of the two ethnic groups (P<0.05 for all). Our study exhibited a correlation between the BDNF rs11030104 SNP and serum TC and LDL-C levels in the Jing males. These results indicate that there may be a racial/ethnic- and/or sex-specific association of the BDNF rs11030104 SNP and serum lipid parameters.

17.
Artigo em Inglês | MEDLINE | ID: mdl-29234402

RESUMO

Hempseed (Cannabis sativa L.) has been used as a health food and folk medicine in China for centuries. In the present study, we sought to define the underlying mechanism by which the extract of Fructus Cannabis (EFC) protects against memory impairment induced by D-galactose in rats. To accelerate aging and induce memory impairment in rats, D-galactose (400 mg/kg) was injected intraperitoneally once daily for 14 weeks. EFC (200 and 400 mg/kg) was simultaneously administered intragastrically once daily in an attempt to slow the aging process. We found that EFC significantly increased the activity of superoxide dismutase, while lowering levels of malondialdehyde in the hippocampus. Moreover, EFC dramatically elevated the organ indices of some organs, including the heart, the liver, the thymus, and the spleen. In addition, EFC improved the behavioral performance of rats treated with D-galactose in the Morris water maze. Furthermore, EFC inhibited the activation of astrocytes and remarkably attenuated phosphorylated tau and suppressed the expression of presenilin 1 in the brain of D-galactose-treated rats. These findings suggested that EFC exhibits beneficial effects on the cognition of aging rats probably by enhancing antioxidant capacity and anti-neuroinflammation, improving immune function, and modulating tau phosphorylation and presenilin expression.

18.
Oncotarget ; 8(41): 70378-70393, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-29050287

RESUMO

Maonan ethnic group is a relatively conservative and isolated minority in China. Little is known about the association of the mevalonate kinase (MVK), methylmalonic aciduria (cobalamin deficiency) cblB type (MMAB) single nucleotide polymorphisms (SNPs) and serum lipid levels. This study aimed to determine the association between four SNPs in the MVK/MMAB and serum lipid levels. Genotyping of the rs3759387, rs877710, rs7134594 and rs9593 SNPs was performed in 1264 Maonan subjects and 1251 Han participants. Allele and genotype frequencies of the selected SNPs were different between the two populations (P < 0.05-0.001). Four SNPs were associated with high-density lipoprotein cholesterol (HDL-C) in the both ethnic groups (P < 0.0125-0.001); and one SNP with apolipoprotein (Apo) A1 (rs7134594) in Han Chinese (P <0.0125). Strong linkage disequilibria were noted among the SNPs (D'=0.63-0.96; r2 =0.13-0.88). The commonest haplotype was C-C-C-T (> 50%). The frequencies of C-C-C-T, C-G-T-A, A-G-T-A, C-G-C-T, and A-C-T-A were different between the two populations (P <0.001). The associations between haplotypes and dyslipidemia were different in the Han and/or Maonan population (P < 0.05-0.001), haplotypes could explain much more serum lipid variation than any single SNP alone especially for HDL-C. Differences in lipid profiles between the two populations might partially attribute to these SNPs and their haplotypes.

19.
Sci Rep ; 7(1): 11626, 2017 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-28912560

RESUMO

Maonan nationality is a relatively conservative and isolated minority in China. Little is known about the association of the Slit-Robo Rho GTPase activating protein 2 gene (SRGAP2) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations. This study was performed to clarify the association of the SRGAP2 rs2483058 and rs2580520 SNPs and their haplotypes with serum lipid traits in the Maonan and Han populations. Genotyping of the 2 SNPs was performed in 2444 unrelated subjects (Han, 1210 and Maonan, 1234) by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The allelic (rs2483058) and genotypic (rs2483058 and rs2580520) frequencies were different between the two ethnic groups. Four haplotypes were identified in our populations, and the rs2483058G-rs2580520C haplotype was the commonest one. The rs2483058C-rs2580520G haplotype was associated with an increased risk of dyslipidemia, and showed consistent association with serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) A1 levels, and the ApoA1/ApoB ratio. These results indicated that the SRGAP2 SNPs and their haplotypes were associated with serum lipid levels. Their haplotypes can explain much more serum lipid variation than any single SNP alone, especially for serum TC, HDL-C and ApoA1 levels.


Assuntos
Alelos , Proteínas Ativadoras de GTPase/genética , Interação Gene-Ambiente , Estudos de Associação Genética , Haplótipos , Lipídeos/sangue , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , China/epidemiologia , China/etnologia , Exposição Ambiental , Feminino , Frequência do Gene , Genótipo , Humanos , Estilo de Vida , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Vigilância da População , Característica Quantitativa Herdável , Análise de Sequência de DNA
20.
BMC Geriatr ; 17(1): 4, 2017 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-28056856

RESUMO

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive performance and the modulation of several metabolic parameters in some disease models, but its potential roles in successful aging remain unclear. We herein sought to define the putative correlation between BDNF Val66Met and several metabolic risk factors including BMI, blood pressure, fasting plasma glucose (FPG) and lipid levels in a long-lived population inhabiting Hongshui River Basin in Guangxi. METHODS: BDNF Val66Met was typed by ARMS-PCR for 487 Zhuang long-lived individuals (age ≥ 90, long-lived group, LG), 593 of their offspring (age 60-77, offspring group, OG) and 582 ethnic-matched healthy controls (aged 60-75, control group, CG) from Hongshui River Basin. The correlations of genotypes with metabolic risks were then determined. RESULTS: As a result, no statistical difference was observed on the distribution of allelic and genotypic frequencies of BDNF Val66Met among the three groups (all P > 0.05) except that AA genotype was dramatically higher in females than in males of CG. The HDL-C level of A allele (GA/AA genotype) carriers was profoundly lower than was non-A (GG genotype) carriers in the total population and the CG (P = 0.009 and 0.006, respectively), which maintained in females, hyperglycemic and normolipidemic subgroup of CG after stratification by gender, BMI, glucose and lipid status. Furthermore, allele A carriers, with a higher systolic blood pressure, exhibited 1.63 folds higher risk than non-A carriers to be overweight in CG (OR = 1.63, 95% CI: 1.05 - 2.55, P = 0.012). Multiple regression analysis displayed that the TC level of LG reversely associated with BDNF Val66Met genotype. CONCLUSIONS: These data suggested that BDNF 66Met may play unfavorable roles in blood pressure and lipid profiles in the general population in Hongshui River area which might in part underscore their poorer survivorship versus the successful aging individuals and their offspring.


Assuntos
Pressão Sanguínea/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Metabolismo dos Lipídeos/genética , Longevidade , Doenças Metabólicas , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Grupos Étnicos , Feminino , Genótipo , Humanos , Longevidade/genética , Longevidade/fisiologia , Masculino , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/genética , Pessoa de Meia-Idade , Polimorfismo Genético
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