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1.
Int J Clin Exp Pathol ; 11(10): 5024-5033, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31949579

RESUMO

Detection of CYP2A6 variant alleles, and knowledge about their allelic frequency in Tibetan ethnic groups, is important to establish the clinical relevance of screening for these polymorphisms to optimize pharmacotherapy. We used DNA sequencing to investigate the promoter, exons and surrounding introns, and untranslated region of the CYP2A6 gene in 100 unrelated healthy Tibetan individuals. We also used SIFT and PolyPhen-2 to predict the protein function of the novel non-synonymous mutation in CYP2A6 coding regions. We found 33 different CYP2A6 polymorphisms in the Tibetan population, five of which were novel: -98T > G in promoter region, 1886C > A, 5640C > A, 5827G > T in intron and missense mutation 5011G > A in exon 7. We identified six CYP2A6 alleles (*1, *10, *11, *14, *15 and *18), with a wide frequency range from 1.00% to 86.50% in the population. We also detected six CYP2A6 genotypes, with a wide frequency range from 2.00% to 73.00%. Three of which (*1/*10, *1/*11 and *1/*18) lead to decreased enzyme activity. This study provided new information regarding CYP2A6genetic polymorphisms in Tibetan individuals, which will greatly facilitate studies on the relevance of pharmacogenetics for CYP2A6 with respect to disease risk and to the pharmacokinetics and pharmacodynamics of many drugs.

2.
Oncotarget ; 8(58): 98417-98425, 2017 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-29228700

RESUMO

Interferon-gamma (IFNG) and its receptor (IFNGR1) are principal genes that associated with tuberculosis. In the current study we aimed to explore the genetic association of polymorphisms of IFNG and IFNGR1 with the risk of pulmonary tuberculosis (PTB) in the Chinese Tibetan population. We selected 467 PTB patients and 503 healthy controls to genotype 9 single nucleotide polymorphisms (SNPs). The unconditional logistic regression analysis was applied for assessing the associations, and the risk of PTB were evaluated by calculating the odds ratio (OR) and 95% confidence interval (CI). The results showed that mutants of rs9376268, rs1327475 and rs1327474 in IFNGR1 played a protective role in the PTB risk under genotype, dominant and additive model (P<0.05). On the contrary, minor allele "A" of rs2069705 in IFNG significantly increased the risk of PTB under genotype, dominant and additive model (P<0.05). However, after Bonferroni's multiple adjustment was applied to our data, which level of significant was set at P<0.0011 (0.05/45). Only variant of rs9376268 was significantly associated decrease the PTB susceptibility under additive model (OR=0.73, 95%CI=0.61-0.88, P<0.001). Furthermore, in the haplotype analysis, we found that the haplotypes "C-G-G-A-C", "C-G-A-G-T" and "T-A-G-G-T" of rs9376267-rs9376268-rs1327475-rs7749390-rs1327474 block were extremely decreased the PTB risk (P<0.01), however, the haplotypes "C-G-G-A-T", "T-G-G-G-T" and "C-G-G-G-T" of the block were extremely increased the PTB risk (P<0.01). These results suggested that variants of IFNGR1 may have a close relation with the PTB risk in Chinese Tibetan population.

3.
Oncotarget ; 8(6): 10523-10530, 2017 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28060765

RESUMO

Single nucleotide polymorphisms (SNPs) in TERT may be associated with susceptibility to esophageal cancer. In this study, we analyzed the association between TERT SNPs and risk of esophageal cancer in 386 esophageal cancer patients and 495 healthy subjects from the Xi'an area of China. Of the four SNPs examined, rs10069690 and rs2242652 were correlated with esophageal cancer risk. Additionally, after adjusting for age and gender, the "Trs10069690Ars2242652", "Trs10069690Grs2242652" haplotypes were associated with an increased risk of esophageal cancer, while the and "Crs10069690Grs2242652" haplotype was associated with a decreased risk of esophageal cancer. These findings suggest that TERT polymorphisms may contribute to the development of esophageal cancer.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Esofágicas/genética , Polimorfismo de Nucleotídeo Único , Telomerase/genética , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , China , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/etnologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Heterozigoto , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Medição de Risco , Fatores de Risco
4.
Oncotarget ; 7(51): 85464-85471, 2016 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-27863428

RESUMO

We investigated the correlation between type 2 diabetes (T2D)-related genes and the clinical characteristics of T2D in the Chinese Han population. Our study included 319 patients and 387 controls. Age, gender, clinical features, medications intake and biochemical blood profiles were analyzed. Genotyping was performed on a total of 18 single nucleotide polymorphisms previously reported to be associated with T2D. Our analyses revealed that the CT genotype of ARHGAP22 rs4838605 is associated with T2D risk. Upon analyzing the subjects' clinical characteristics, we found that for rs2811893, the TT genotype correlated with high creatinine levels, while the AA genotype of rs17045754 and the TT genotype of rs4838605 correlated with elevated triglyceride levels. In addition, the AA genotype of rs17376456 and the TT genotype of rs6214 (p = 0.006) correlated with elevated hemoglobin A1c levels. Lastly, those carrying the TT genotype of rs7772697 and the CA genotype of rs3918227 exhibited higher mean body mass index and Cystatin C than controls. Our results showing that the ARHGAP22 gene is associated with an increased risk of T2D, and that seven SNPs in MYSM1, PLXDC2, ARHGAP22 and HS6ST3 promote T2D progression and could help predict the clinical course of T2D in patients at risk.


Assuntos
Diabetes Mellitus Tipo 2/genética , Polimorfismo de Nucleotídeo Único , Idoso , Povo Asiático/genética , Biomarcadores/sangue , Estudos de Casos e Controles , China , Creatinina/sangue , Cistatina C/análise , Proteínas de Ligação a DNA/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/etnologia , Progressão da Doença , Feminino , Proteínas Ativadoras de GTPase/genética , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Hemoglobinas Glicadas/análise , Heterozigoto , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Receptores de Superfície Celular/genética , Fatores de Risco , Sulfotransferases/genética , Transativadores , Fatores de Transcrição/genética , Triglicerídeos/sangue , Proteases Específicas de Ubiquitina
5.
Oncotarget ; 7(48): 79596-79604, 2016 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-27793000

RESUMO

Laryngeal squamous cell carcinoma (LSCC) is one of the most common and aggressive malignancies of the upper digestive tract. The present study is a retrospective analysis of data from a prospective longitudinal study. A total of 170 male LSCC patients (average age, 60.75±10.082) at the First Affiliated Hospital of Xi'an Jiaotong University School of Medicine were recruited between January 2002 and April 2013 for this study. We assessed correlations between patient characteristics and survival, and sequenced genomic DNA from patient peripheral blood samples. We found that the single nucleotide polymorphisms (SNPs), rs11903757, with closest proximity to NABP1 and SDPR, and rs966423 in DIRC3, were associated with survival in LSCC patients. Median follow-up was 38 months (range 3-122) and median survival time was 48 months. LSCC patients with total laryngectomy, poor differentiation, T3-T4 stage, N1-N2 stage or III-IV TNM stage had reduced survival. This is the first study to demonstrate that the rs11903757 GT (HR=2.036; 95% CI, 1.071-3.872; p=0.030) and rs966423 TT (HR=11.677; 95% CI, 3.901-34.950; p=0.000) genotypes predict poor patient outcome. These polymorphisms may serve as useful clinical markers to predict patient survival, and to guide individual patient therapeutic decisions.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias Laríngeas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Diferenciação Celular , Distribuição de Qui-Quadrado , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/cirurgia , Heterozigoto , Homozigoto , Humanos , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/cirurgia , Laringectomia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Fenótipo , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fatores de Tempo , Resultado do Tratamento
6.
Oncotarget ; 7(44): 71703-71709, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27765935

RESUMO

We examined the multigenetic index on the progression of laryngeal carcinoma in Chinese population. This study aims to assess the effects of single nucleotide polymorphisms (SNPs) on survival of Laryngeal Carcinoma (LC) patients. Eighteen SNPs were selected and genotyped using the Sequenom iPLEX genotyping system in a cohort of 170 resected Chinese LC patients. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. Overall, the median survival time (MST) was 38.00 months. The one, three and five year Kaplan-Meier survival rate was 0.847 ± 0.028, 0.572 ± 0.038 and 0.471 ± 0.041 respectively. The risks of death with the Hazard Ratio (HR) [95% confidence intervals] (CI) of 2.40 (1.15-4.50), 2.17 (1.45-3.25), 2.39 (1.58-3.62), 3.29 (2.10-5.18), respectively. There was significant associations between the SNPs and OS when the entire study population was examined. The rs1321311 TG genotype (vs.GG), rs2494938 AA genotype (vs. GG) and rs9363918 TG genotype (vs. GG) were associated with a worse prognosis for OS (adjusted HR = 1.64; 95%confidence interval = 1.07-2.51; P = 0.022, adjusted HR = 2.85; P =0.12; adjusted HR = 1.78; P = 0.009; respectively).The results suggest for the first time that these gene polymorphisms may serve as an independent prognostic marker for LC patients.


Assuntos
Neoplasias Laríngeas/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidor de Quinase Dependente de Ciclina p21/genética , Genótipo , Humanos , Neoplasias Laríngeas/mortalidade , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Ubiquitina-Proteína Ligases/genética
7.
Oncotarget ; 7(45): 73781-73791, 2016 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-27655710

RESUMO

High rates of recurrence and the lack of effective treatments contribute to the poor prognosis of patients with glioma. There is therefore an urgent need for an easily detectable biomarker to facilitate early detection. In this study, we explored the association between TERT rs2853676 genetic polymorphisms and the prognosis of Chinese glioma patients. A total of 481 glioma patients at the Tangdu Hospital of the Fourth Military Medical University in China were included in this study. The overall survival rates were calculated using the Kaplan-Meier method. Prognostic factors were determined through multivariate Cox regression analysis. The overall survival (OS) rates of one, two, and three years were 31%, 10.3%, and 7.5%, respectively. The progress-free survival (PFS) rates of one, two, and three years were 15.7%, 7.3%, and 4.7%, respectively. The genotype "A/G" of TERT rs2857676 decreased the PFS rate (hazard ratios [HR] = 0.824; P = 0.059). The genotype "A/G (HR = 0.803; 95% CI, 0.656 - 0.982; P = 0.032)" and "A/A + A/G" decreased the recurrence rate compared to the genotype G/G (HR = 0.818; 95% CI, 0.675-0.99; P = 0.040). Our study indicates that TERT rs2853676 polymorphisms correlate with glioma survival and recurrence rates in a Chinese population, which suggests that they could potentially serve as prognostic markers in glioma patients.


Assuntos
Alelos , Povo Asiático/genética , Predisposição Genética para Doença , Glioma/genética , Glioma/mortalidade , Polimorfismo de Nucleotídeo Único , Telomerase/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China , Terapia Combinada , Feminino , Genótipo , Glioma/patologia , Glioma/terapia , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Adulto Jovem
8.
BMC Infect Dis ; 16: 469, 2016 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-27595605

RESUMO

BACKGROUND: The vitamin D receptor (VDR) mediates the immunological function of vitamin D3, which activates macrophages, and vitamin D deficiency has been linked to tuberculosis risk. Single nucleotide polymorphisms (SNPs) in VDR may influence the function of vitamin D and susceptibility to tuberculosis. METHODS: This study included 217 patients with pulmonary tuberculosis (PTB) and 383 healthy subjects in a Tibetan Chinese population living in and near Xi'an. Association analyses of SNPs in VDR were performed with the SPSS 17.0 statistical packages, SNP stats software, Haploview software package (version 4.2), and the SHEsis software platform. RESULTS: Our results revealed a correlation between three SNPs (rs11574143, odds ratio [OR]: 1.47, 95 % confidence interval [CI]: 1.11 - 1.94, p = 0.006, p-adjust = 0.030; rs11574079, OR: 0.48, 95 % CI: 0.25 - 0.92, p = 0.023, p-adjust = 0.115; rs11168287, OR: 2.55, 95 % CI: 2.00 - 3.25, p = 1.730E-14, p-adjust = 0.865E-13) and PTB based on Chi-square tests. We observed the allele "A" of rs11574143 and rs11168287 increased the PTB risk and the allele "A" of rs11574079 provided a protective effect against PTB. CONCLUSIONS: The goal of this study was the identification of putative associations between five SNPs (rs11574143, rs7975232, rs11574079, rs3819545 and rs11168287) in VDR and susceptibility to PTB. Our findings demonstrated associations between VDR polymorphisms and PTB development.


Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Tuberculose Pulmonar/epidemiologia , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Tibet/etnologia , Tuberculose Pulmonar/genética
9.
Oncotarget ; 7(34): 54771-54781, 2016 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-27458158

RESUMO

We investigated the associations between single nucleotide polymorphisms (SNPs) in the testis-specific Y-encoded-like protein 6 (TSPYL6) gene and breast cancer (BC) susceptibility in the Han Chinese population. A total of 183 BC patients and 195 healthy women were included in the study. Six SNPs in TSPYL6 were genotyped and the association with BC risk analyzed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analysis. Multivariate logistic regression analysis was used to identify SNPs that correlated with BC susceptibility. Rs11896604 was associated with a decreased risk of BC based on dominant and genotype models. Rs843706 was associated with an increased risk of BC based on a recessive model. Rs11125529 was associated with decreased BC susceptibility based on a genotype model. Finally, rs843711 inversely correlated with clinical stage III/IV BC. Our findings reveal a significant association between SNPs in the TSPYL6 gene and BC risk in a Han Chinese population.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Adulto , Povo Asiático/genética , Neoplasias da Mama/etnologia , Neoplasias da Mama/patologia , China , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias
10.
Am J Med Genet B Neuropsychiatr Genet ; 171(8): 1006-1012, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27103199

RESUMO

Schizophrenia (SCZ) is a complex and severe mental disorder with highly heritability (80%). Several large genome-wide association studies have identified that the transcription factor 4 (TCF4) polymorphisms were strongly associated with SCZ. Therefore, the present study was to replicate the potential relationships between the TCF4 polymorphisms and SCZ. Furthermore, the study also investigated whether other variants were associated with SCZ in the Han Chinese. We conducted a case-control study including 499 patients and 500 healthy controls. Five SNPs were successfully genotyped and evaluated the association with SCZ by using χ2 test and genetic model analysis. We found that the genotype "AG" of rs9320010 and "GA" of rs7235757 decreased SCZ risk (OR = 0.70, 95%CI = 0.50-0.99, P = 0.041; OR = 0.69, 95%CI = 0.49-0.97, P = 0.034, respectively). In the genetic model analysis, we also observed that the allele "A" of rs9320010 and "G" of rs7235757 were inversely related with the risk of SCZ in the dominant model (OR = 0.72, 95%CI = 0.52-0.98, P = 0.039; OR = 0.69, 95%CI = 0.50-0.96, P = 0.025, respectively). Further interaction and stratification analysis suggested that rs1452787 was notably correlated with increased SCZ risk in males (OR = 2.77, 95%CI = 1.43-5.35, P = 0.002). Our study indicated that rs9320010, rs7235757, and rs1452787 were prominently associated with SCZ. Further studies are required to verify our findings and focus on determining the biological functions of the SNPs. © 2016 Wiley Periodicals, Inc.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Esquizofrenia/genética , Fatores de Transcrição/genética , Adulto , Alelos , Povo Asiático/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Estudos de Casos e Controles , China , Etnicidade/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco , Fator de Transcrição 4 , Fatores de Transcrição/metabolismo
11.
Xenobiotica ; 46(9): 850-6, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26739429

RESUMO

1. Detection of CYP3A5 variant alleles, and knowledge about their allelic frequency in Uyghur ethnic groups, is important to establish the clinical relevance of screening for these polymorphisms to optimize pharmacotherapy. 2. We used DNA sequencing to investigate the promoter, exons and surrounding introns, and 3'-untranslated region of the CYP3A5 gene in 96 unrelated healthy Uyghur individuals. We also used SIFT and PolyPhen-2 to predict the protein function of the novel non-synonymous mutation in CYP3A5 coding regions. 3. We found 24 different CYP3A5 polymorphisms in the Uyghur population, three of which were novel: the synonymous mutation 43C > T in exon 1, two mutations 32120C > G and 32245T > C in 3'-untranslated region, and we detected the allele frequencies of CYP3A5*1 and *3 as 64.58% and 35.42%, respectively. While no subjects with CYP3A5*6 were identified. Other identified genotypes included the heterozygous genotype 1A/3A (59.38%) and 1A/3E (11.46%), which lead to decreased enzyme activity. In addition, the frequency of haplotype "TTAGGT" was the most prevalent with 0.781. 4. Our data provide new information regarding CYP3A5 genetic polymorphisms in Uyghur individuals, which may help to improve individualization of drug therapy and offer a preliminary basis for more rational use of drugs.


Assuntos
Citocromo P-450 CYP3A/genética , Polimorfismo de Nucleotídeo Único , Povo Asiático , China , Citocromo P-450 CYP3A/metabolismo , Frequência do Gene , Genótipo , Haplótipos , Humanos
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