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1.
Clin Chim Acta ; 501: 66-71, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31756311

RESUMO

OBJECTIVE: To screen long non-coding RNA (lncRNA) related to glucokinase regulatory protein gene (GCKR), its differential expression was analyzed in patients with Type 2 diabetes mellitus (T2DM) and control samples. The correlation of lncRNA with GCKR was verified and its potential value as a molecular marker of T2DM was assessed. METHODS: Lymphocyte RNA was extracted from five patients with T2DM and five patients with non-T2DM. The expression profiles of circulating lncRNAs and mRNAs were obtained by microarray. Bioinformatics analysis was used to screen lncRNAs associated with the GCKR gene in 127 patients with T2DM and 130 patients with non-T2DM were selected. The expression levels of the GCKR gene and lncRNA (ENST00000588707.1 and TCONS_00004187) in the T2DM group and control group were verified by real-time PCR. Additionally, a correlation analysis was conducted. The value of circulating ENST00000588707.1 and TCONS_00004187 as biomarkers for the diagnosis of T2DM was performed by receiver operating characteristic curve analysis. RESULTS: We identified 68 lncRNAs and 74 mRNAs differentially expressed from the expression profile. Compared with the control group, the expression levels of the GCKR gene and lncRNA ENST00000588707.1 and TCONS_00004187 in the T2DM group were significantly lower (P < 0.05). The correlation analysis revealed that ENST00000588707.1 and TCONS_00004187 were correlated with GCKR gene expression and glycolipid metabolism (P < 0.05). ROC analysis showed that the area under the curve value of ENST00000588707.1 between T2DM patients and non-T2DM patients was 0.816 (95% CI: 0.764-0.869, sensitivity 72.0%, specificity 80.3%) and the AUC value of TCONS_00004187 was 0.826 (95% CI: 0.774-0.879, sensitivity 81.6%, specificity 61.3%). CONCLUSION: lncRNA ENST0000588707.1 and TCONS_00004187 could serve as potential biomarkers for T2DM, which could involve in glycolipid metabolism by regulating the GCKR gene.

3.
PLoS One ; 11(9): e0162611, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27622506

RESUMO

BACKGROUND: Diabetes is a major global public health problem driven by a high prevalence of metabolic risk factors. OBJECTIVE: To describe the differences of metabolic risk factors of type 2 diabetes, as well as glycemic control and complicated diabetic complications between rural and urban Uygur residents in Xinjiang Uygur Autonomous Region of China. METHODS: This comparative cross-sectional study, conducted among 2879 urban and 918 rural participants in Xinjiang, China, assessed the metabolic risk factors of diabetes and related complications differences between urban and rural settlements. RESULTS: Compared to rural areas, urban participants had higher education level and more average income, little physical activity, less triglycerides and higher HDL-c (p < 0.05 respectively). Differences in metabolic risk factors by urban/rural residence included overweight or obesity, triglycerides (≥1.71mmol/l), HDL-c (< 1.04 mmol/l), alcohol intake, and physical inactivity (p < 0.01 respectively). There was significant difference regarding the prevalence of HbA1c >8% (48.1% versus 54.5%, p = 0.019) between rural and urban diabetic participants. No significant difference in the prevalence of type 2 diabetic complications between urban and rural participants (74.9% versus 72.2%; p = 0.263) was detected. Compared to rural participants, the most prevalent modifiable risk factors associated with diabetic complications in urban participants were obesity (BMI ≥ 28 Kg/m2), HDL-c (< 1.04 mmol/l), physical inactivity and irregular eating habits (p = 0.035, p = 0.001, p < 0.001, and p = 0.013, respectively). CONCLUSIONS: Urban settlers were significantly more likely to have metabolic risk factors highlighting the need for public health efforts to improve health outcomes for these vulnerable populations. Diabetes related complications risk factors were prevalent amongst rural and urban diabetes settlers.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Adulto , Idoso , Índice de Massa Corporal , China , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Rural , População Urbana , Adulto Jovem
4.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 33(4): 540-4, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-27455017

RESUMO

OBJECTIVE: To assess the association of glucokinase regulator protein (GCKR) gene polymorphisms and type 2 diabetes (T2D) among ethnic Uygurs from Xinjiang, China. METHODS: One thousand and six T2D patients and 1004 healthy controls were recruited. The rs780094 genotype of the GCKR gene was determined with a Sequenom Mass ARRAY system. RESULTS: The distribution of GCKR rs780094 AA, AG and GG genotypes were not statistically different between the two groups (P>0.05). After adjusting confounding factors, an association of rs780094 with T2D was observed in an additive and dominant model (OR=1.181, 95%CI: 1.021-1.366, P=0.025; OR=1.296, 95%CI: 1.043-1.610, P=0.019). The total cholesterol level was higher in AA carriers than GG and GA carriers (P<0.05). CONCLUSION: The AA genotype of the GCKR rs780094 polymorphism may increase the risk of T2D among ethnic Uygurs from Xinjiang.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Diabetes Mellitus Tipo 2/genética , Polimorfismo Genético , China/etnologia , Colesterol/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Genótipo , Humanos , Modelos Logísticos
5.
Med Sci Monit ; 22: 474-87, 2016 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-26873362

RESUMO

BACKGROUND We investigated the association between 8 single-nucleotide polymorphisms (SNPs) at 3 genetic loci (CDKAL1, CDKN2A/2B and FTO) with type 2 diabetes (T2D) in a Uyghur population. MATERIAL AND METHODS A case-control study of 879 Uyghur patients with T2D and 895 non-diabetic Uyghur controls was conducted at the Hospital of Xinjiang Medical University between 2010 and 2013. Eight SNPs in CDKAL1, CDKN2A/2B and FTO were analyzed using Sequenom MassARRAY®SNP genotyping. Factors associated with T2D were assessed by logistic regression analyses. Gene-gene and gene-environment interactions were analyzed by generalized multifactor dimensionality reduction. RESULTS Genotype distributions of rs10811661 (CDKN2A/2B), rs7195539, rs8050136, and rs9939609 (FTO) and allele frequencies of rs8050136 and rs9939609 differed significantly between diabetes and control groups (all P<0.05). While rs10811661, rs8050136, and rs9939609 were eliminated after adjusting for covariates (P>0.05), rs7195539 distribution differed significantly in co-dominant and dominant models (P<0.05). In gene-gene interaction analysis, after adjusting for covariates the two-locus rs10811661-rs7195539 interaction model had a cross-validation consistency of 10/10 and the highest balanced accuracy of 0.5483 (P=0.014). In gene-environment interaction analysis, the 3-locus interaction model TG-HDL-family history of diabetes had a cross-validation consistency of 10/10 and the highest balanced accuracy of 0.7072 (P<0.001). The 4-locus interaction model, rs7195539-TG-HDL-family history of diabetes had a cross-validation consistency of 8/10 (P<0.001). CONCLUSIONS Polymorphisms in CDKN2A/2B and FTO, but not CDKAL1, may be associated with T2D, and alleles rs8050136 and rs9939609 are likely risk alleles for T2D in this population. There were potential interactions among CDKN2A/2B (rs10811661) - FTO (rs7195539) or FTO (rs7195539)-TG-HDL-family history of diabetes in the pathogenesis of T2D in a Uyghur population.


Assuntos
Diabetes Mellitus Tipo 2/genética , Interação Gene-Ambiente , Adulto , Idoso , Alelos , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Feminino , Genes p16 , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Adulto Jovem , tRNA Metiltransferases/genética
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 32(6): 881-5, 2015 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-26663070

RESUMO

OBJECTIVE: To investigate the correlation between polymorphisms of uric acid transporter related gene SLC17A1 and hyperuricemia (HUA) among ethnic Uygur patients from Xinjiang. METHODS: A case-control study was carried out, which enrolled 1036 patients with hyperuricemia and 1031 healthy controls. Two single nucleotide polymorphisms (SNPs) of the SLC17A1 gene were determined with Sequenom MassARRAY. Crossover analysis was used to assess the effect of interaction between above SNPs and alcohol drinking on uric acid level. RESULTS: Genotypic and allelic frequencies of the SLC17A1 gene at the two loci in the two groups were compared. The CT genotype of the rs9467596 locus and TC genotype of the rs2096386 locus showed a higher risk for hyperuricemia (OR=1.334, 95%CI:1.082-1.644; OR=1.242, 95%CI:1.015-1.519, respectively). Crossover analysis also revealed that the SLC17A1 rs2096386 polymorphism has a positive interaction with alcohol drinking in a multiplication model (ORint=1.21, P<0.05, OR>1). CONCLUSION: SNP rs9467596 and rs2096386 of the SLC17A1 gene may have a correlation between hyperuricemia and alcohol drinking among Uygur patients.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Predisposição Genética para Doença/genética , Hiperuricemia/genética , Polimorfismo de Nucleotídeo Único , Proteínas Cotransportadoras de Sódio-Fosfato Tipo I/genética , Adulto , Idoso , Consumo de Bebidas Alcoólicas/etnologia , Alelos , Grupo com Ancestrais do Continente Asiático/genética , China , Grupos Étnicos/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Hiperuricemia/etnologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Adulto Jovem
7.
Genet Test Mol Biomarkers ; 19(12): 698-702, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26540651

RESUMO

OBJECTIVE: To investigate the association between KCNQ1 gene polymorphisms and type 2 diabetes (T2D) in an admixed ethnic minority, Uyghur population, living in the Northwest region of China. MATERIALS AND METHODS: We genotyped three tagging single-nucleotide polymorphisms rs2283171, rs11023485, and rs2283208 of the KCNQ1 gene in 1006 T2D participants and 1004 controls and conducted association analysis. RESULTS: The frequencies of the AG and GG genotypes and the G allele of rs2283171 were higher in the control group (51.4%, 22%, and 47.7%, respectively) than in the case group (49%, 17.6%, and 42.1%, respectively). The minor G allele decreased the risk of T2D with a per-allele odds ratio of 0.79 (95% CI: 0.70-0.90) for the additive genetic model in univariate analysis (p = 0.0001). After adjustment for the covariates of age, gender, smoking, alcohol use, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), triglyceride (TG), and total cholesterol (TC), the diabetic protective effect of the rs2283171-G allele remained. No difference was observed in the frequency distributions of the rs11023485 and rs2283208 genotypes between the two groups. CONCLUSION: We identified a novel association between rs2283171 of KCNQ1 and T2D in the Uyghur population. Further association and functional studies are required to identify the causal functional variant that is in linkage disequilibrium with this polymorphism.


Assuntos
Alelos , Diabetes Mellitus Tipo 2/genética , Frequência do Gene , Canal de Potássio KCNQ1/genética , Polimorfismo de Nucleotídeo Único , Adulto , Grupo com Ancestrais do Continente Asiático/etnologia , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/etnologia , Diabetes Mellitus Tipo 2/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
8.
Int J Environ Res Public Health ; 12(9): 11797-814, 2015 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-26393635

RESUMO

BACKGROUND: Genetic polymorphisms of the transcription factor 7-like 2 (TCF7L2) gene have been reported to be strongly associated with type 2 diabetes mellitus (T2DM) in Icelandic, Danish and American populations and further replicated in other European populations, African Americans, Mexican Americans, and Asian populations. The aim of the present study was to investigate the association of TCF7L2 gene polymorphisms with T2DM in a Uygur population of China. METHODS: 877 T2DM patients and 871 controls were selected for the present study. Two single nucleotide polymorphisms (SNPs) (rs12255372 and rs7901695) were genotyped by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. The associations of SNPs and haplotypes with T2DM and linkage disequilibrium (LD) structure of the TCF7L2 gene were analyzed. RESULTS: For total participants and male, the distribution of rs12255372 alleles and the dominant model (Guanine Guanine (GG) genotype vs. Guanine Thymine (GT) genotype + Thymine Thymine (TT) genotype) showed significant difference between T2DM and control subjects (for allele: p = 0.013 and p = 0.002, respectively; for dominant model: p = 0.028 and p = 0.008, respectively). The distribution of rs7901695 alleles and the dominant model (TT genotype vs. Thymine Cytosine (TC) genotype + Cytosine Cytosine (CC) genotype) for total participants and male showed significant difference between T2DM and control subjects (for allele: both p = 0.001; for dominant model: p = 0.006 and p = 0.008, respectively). CONCLUSIONS: Our data suggested that the genetic polymorphisms of the TCF7L2 gene were associated with T2DM in the Uygur population of China.


Assuntos
Diabetes Mellitus Tipo 2/etnologia , Haplótipos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética , Adulto , China , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 2 Semelhante ao Fator 7 de Transcrição/metabolismo
9.
Int J Clin Exp Pathol ; 8(7): 8260-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26339395

RESUMO

BACKGROUND: The overall objective of this study was to investigate neuronal apoptosis and expression of apoptosis related proteins (c-jun, cytc and Bax) in the cerebellum of rates with heroin addiction. MATERIAL/METHODS: 40 adult male Sprague-Dawley rats which weighing 200-220 g were randomly divided into 5 groups (n = 8 per group): control group, 10-day heroin-addicted group, 20-day heroin-addicted group, 30-day heroin-addicted group and 40-day heroin-addicted group. Rats in the control group were treated with normal saline. Rats in the addiction groups (20 d, 30 d, 40 d) were all given subcutaneous injection with heroin for 15 days to induce heroin addiction. After injected with heroin for 15 days, rats were treated with naloxone at a dose of 5 mg/kg to induce abstinence for 30 mins to examine the addiction of rats. They were then continued to be treated with heroin for another 10 days, 20 days, 30 days, and 40 days respectively to establish heroin-addicted models. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was employed to identify apoptotic cells [6]. Immunohistochemistry and Western blot assay were also used in the study to examine the protein expressions of c-jun, cytc and Bax in the cerebellum. RESULTS: Compared with the control group, the proportion of apoptotic neurons increased significantly in the heroin addiction groups (10 d, 20 d, 30 d, 40 d) (P < 0.05), also accompanied by markedly increased expressions of c-jun, cytc and Bax (P < 0.05) depending on doses of heroin in the cerebellum. Thus, the significant differences were observed in heroin addiction groups (10 d, 20 d,30 d, 40 d) and control group (P < 0.05). CONCLUSION: Long-term use of heroin may induce neuronal apoptosis in the cerebellum by raising the expressions of pro-apoptotic c-jun, cytc and Bax, which might be one of mechanisms underlying the heroin-induced cerebellum neuronal damage.


Assuntos
Apoptose , Cerebelo/patologia , Dependência de Heroína/patologia , Neurônios/patologia , Animais , Biomarcadores/metabolismo , Western Blotting , Cerebelo/metabolismo , Citocromos c/metabolismo , Modelos Animais de Doenças , Dependência de Heroína/metabolismo , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Ratos Sprague-Dawley , Fatores de Tempo , Proteína X Associada a bcl-2/metabolismo
10.
Zhonghua Liu Xing Bing Xue Za Zhi ; 36(10): 1167-71, 2015 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-26837367

RESUMO

OBJECTIVE: To explore the relationship between the polymorphism of solute carrier family 30, member 8 (SLC30A8) gene and type 2 diabetes mellitus (T2DM) in Uyhgur in Xinjiang and further analyze the interaction between SLC30A8 gene polymorphism loci and smoking. METHODS: A case control study, including 1 000 patients with T2DM and 1 010 non-diabetic controls, was conducted in Xinjiang. All the subjects were Uygur and the age difference between the two groups was within 3 years. Physical examination and blood biochemical detection were performed to obtain personal clinical parameters. Genomic DNA was extracted from peripheral blood leukocytes. The single nucleotide polymorphism (SNP) of SLC30A8 of all the subjects was tested by using MALDI-TOF. Statistical analyses were performed with SPSS 16.0. Bootstrap method was used to calculate 95% confidence intervals of RERI, AP and S. RESULTS: After adjusting BMI, SBP, TC, HDL-C and LDL-C, rs13266634 of SLC30A8 gene genotype frequency and allele frequency distribution had statistical differences (P<0.05). Rs13266634 of risk allele were C, OR was 1.194 (95% CI: 1.044-1.366). In addition, the data from genotype distribution analysis under different models showed that significant association between rs13266634 and T2DM in dominant model, OR was 1.640 (95% CI 1.072-2.510). The product of rs13266634 with the active smoking or passive smoking had no statistical significance (P>0.05) , indicating there were no multiplication interaction among them. Additive interactions index of RERI, AP and S and its 95% confidence interval of rs13266634 and active smoking, rs13266634 and passive smoking were 0.301 (-1.314-0.712), 0.204 (-0.854-0.446), 0.612 (0.186-2.013) and 0.125 (-0.805-1.055), 0.052 (-0.353-0.456), 1.096 (0.500-2.403) respectively, indicating there were no significant additive interaction among them. CONCLUSION: Rs13666334 of SLC30A8 gene is associated with the susceptibility of T2DM in Uygur, and its protective genotype might be TT. Passive smoking might increase the risk of T2DM in Uygur.


Assuntos
Proteínas de Transporte de Cátions/genética , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Fumar/epidemiologia , Alelos , Estudos de Casos e Controles , China/epidemiologia , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Transportador 8 de Zinco
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