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1.
Zhonghua Nei Ke Za Zhi ; 59(1): 35-39, 2020 Jan 01.
Artigo em Chinês | MEDLINE | ID: mdl-31887834

RESUMO

Objective: To explore the relationship between driver gene mutation (JAK2, MPL and CALR) and disease type in BCR-ABL negative myeloproliferative neoplasms (MPNs) including primary myeloid fibrosis (PMF), essential thrombocytosis (ET) and polycythemia vera (PV). Methods: A total of 32 MPN related genes were detected by high-throughput sequencing in 156 MPN patients. The relationships between disease type and patients' general performance, the characteristics of driver gene mutations, concomitant gene mutations were analyzed. Results: In the population with JAK2 V617F positive mutation, the proportion of patients over 60 years old in PMF was higher than that with ET or PV. By high-throughput sequencing, 22 concomitant gene mutations were detected in 46 patients with JAK2, MPL or CALR mutations, including 4 (8.3%) in PV, 20 (29.4%) in ET, and 22 (55.0%) in PMF. DNMT3A mutation was detected only in patients with PV, while splicing factor related genes including SF3B1, SRSF2 and U2AF1 were only accompanied by PMF. According to the variation allele frequency (VAF) value of JAK2 V617F mutation, the VAF value associated with PV was the highest (68.15%), followed by PMF (37.7%) and ET (23%). However, there were significant differences in the incidence of JAK2 V617F homozygous among 3 different diseases. In patients with JAK2 mutation, the proportion of other gene mutations in PV and ET was significantly lower than that in PMF. Conclusions: Under the condition of common driver gene mutations (JAK2, MPL and CALR), patients' age, VAF value and homozygous state, concomitant gene mutations are closely related to different disease type. These correlations help to improve clinical understanding of disease characteristics and risk assessment.


Assuntos
Calreticulina/genética , Proteínas de Fusão bcr-abl/genética , Janus Quinase 2/genética , Transtornos Mieloproliferativos/genética , Receptores de Trombopoetina/genética , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático/genética , Calreticulina/metabolismo , Feminino , Proteínas de Fusão bcr-abl/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Janus Quinase 2/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Transtornos Mieloproliferativos/sangue , Transtornos Mieloproliferativos/metabolismo , Policitemia Vera/genética , Mielofibrose Primária/genética , Receptores de Trombopoetina/metabolismo , Trombocitemia Essencial/genética
2.
Medicine (Baltimore) ; 98(52): e18523, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876746

RESUMO

Prostate cancer (PCa) is a frequently diagnosed malignant solid tumor in men. The etiology of PCa has been attributed to both environmental and genetic factors. In recent years, many studies have reported that miRNA gene single-nucleotide polymorphisms (SNPs) influence the susceptibility to several diseases such as cancer. To date, the mechanisms of PCa have remained unknown. The main aim of this study was to evaluate the association between PCa susceptibility and miRNA gene SNPs. A total of 156 PCa cases and 188 control subjects were included in this case-control study. The data were collected from hospitalized cases. We collected the demographic characteristic information, which included age, body mass index, tobacco smoking, alcohol consumption, and family history of cancer. Polymorphisms were analyzed by the ligase detection reaction. Unconditional logistic and stratified analyses were used to analyze the association between these SNPs and PCa susceptibility and to calculate the adjusted odds ratios (ORs) and the 95% confidence intervals (CIs). Cox regression model and the log-rank test were used to test the association between genetic variants and the overall survival. We found that miR-23a gene polymorphism rs3745453 carrying CC homozygotes had a 4.16-fold increased risk (95% CI = 1.30-13.25) than those carrying the TT/CT genotypes (P = .02), and the C allele displayed a higher prevalence of PCa than the T allele (OR = 1.68, 95% CI = 1.16-2.45, P = .01). Moreover, miR-23a showed that the homozygous carriers of the C-variant significantly increased the risk of survival rate as compared to the carriers of the TT/CT genotype (OR = 9.67, 95% CI = 2.83-33.09, P = .001). The rs3745453 polymorphism was potentially associated with PCa in the Chinese Han population and had an interactive relationship with the environmental factors.


Assuntos
Predisposição Genética para Doença/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias da Próstata/genética , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Homozigoto , Humanos , Masculino , Neoplasias da Próstata/epidemiologia , Fatores de Risco
3.
Medicine (Baltimore) ; 98(52): e18606, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31876763

RESUMO

The aim of the present study was to examine the association between vascular endothelial growth factor receptor 2 (VEGFR2) rs11941492 C/T polymorphism and rheumatoid arthritis (RA) risk in an eastern Chinese Han population. We examined VEGFR2 rs11941492 C/T polymorphism in 615 RA patients and 839 controls in an East Chinese Han population. The power analysis was used for evaluating the reliability of the results. Genotyping was performed using a custom-by-design 48-Plex single nucleotide polymorphism scan Kit. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression.Our results indicated that VEGFR2 rs11941492 C/T polymorphism (TT vs CC, P = .012, OR = 0.61, 95% CI = 0.41-0.89; TT vs CT + CC, P = .017, OR = 0.63, 95% CI = 0.43-0.92) was associated with a significantly decreased risk of RA. The power analysis showed that this study had a power of 98.5% to detect the effect of rs11941492 C/T polymorphism on RA susceptibility, assuming an OR of 0.61. After stratification analysis, a decreased risk of RA was associated with VEGFR2 rs11941492 TT genotype (TT vs CC) among female patients (TT vs CC, P = .007, OR = 0.53, 95% CI = 0.33-0.84), older patients (Yr ≥55) (TT vs CC, P = .039, OR = 0.58, 95% CI = 0.35-0.97), C-reactive protein-positive patients, anti-cyclic citrullinated peptide antibody-negative patients, rheumatoid factor-positive patients (TT vs CT + CC, P = .015, OR = 0.60, 95% CI = 0.39-0.90), functional class III + IV patients, patients with a DAS28 of ≥3.20, and those with an erythrocyte sedimentation rate of <25. However, our results were obtained from only a moderate-sized sample. Studies with larger sample sizes in other ethnic populations are needed to confirm these results. The VEGFR2 rs11941492 genotype is associated with decreased susceptibility to RA.


Assuntos
Artrite Reumatoide/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Feminino , Predisposição Genética para Doença/genética , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances
4.
Medicine (Baltimore) ; 98(44): e17722, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689810

RESUMO

BACKGROUND: Ulcerative colitis (UC) and Crohn disease (CD) are the 2 main types of inflammatory bowel diseases (IBDs). Several studies have been conducted to investigate the association of Glutathione S-Transferase M1 (GSTM1) null genotype with UC and CD, but the results are inconsistent. Here, we performed a meta-analysis to clarify this controversy based on relative large sample size. METHODS: A systematic article searching was conducted in the PubMed, EMBASE, SCOPUS, WOS, ProQuest, Chinese National Knowledge Infrastructure (CNKI), and Chinese Wanfang databases up to August 31, 2019. Meta-analysis results were synthesized by using crude odds ratio (OR) with its 95% confidence interval (CI). Heterogeneity, sensitivity analysis, subgroup analysis, and publication bias were assessed by using STATA 11.0 software. RESULTS: A total of 15 relevant studies including 4353 IBDs patients (1848 CD cases, 2505 UC cases) and 5413 controls were included in this meta-analysis. Totally, we found a significant association between GSTM1 null genotype and risk to IBDs in the overall populations (OR = 1.37, 95%CI = 1.13-1.65, P = .001). Stratified by ethnicity, we found a significant association between GSTM1 null genotype and risk to IBDs in the Asian population (OR = 2.54, 95%CI = 2.15-3.00, P = .001), but not in the Caucasian population. Stratified by disease type, we found a significant association between GSTM1 null genotype with CD in the Asian population (OR = 2.37, 95%CI = 1.11-5.06, P = .026), and with UC in the Asian (OR = 2.48, 95%CI = 1.93-3.20, P = .001) population. In addition, funnel plot and Egger linear regression test suggests no publication bias in all genetic models. CONCLUSION: GSTM1 null genotype is associated with susceptibility to IBD, UC, and CD in the Asian population. Further well-designed studies are still needed to confirm these findings.


Assuntos
Colite Ulcerativa/genética , Doença de Crohn/genética , Predisposição Genética para Doença/genética , Glutationa Transferase/genética , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genótipo , Humanos , Masculino , Razão de Chances
5.
Medicine (Baltimore) ; 98(44): e17821, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689868

RESUMO

Although many genetic variants related to anti-tuberculosis drug induced liver injury (ATDILI) have been identified, the prediction and personalized treatment of ATDILI have failed to achieve, indicating there remains an area for further exploration. This study aimed to explore the influence of single nucleotide polymorphisms (SNPs) in Bradykinin receptor B2 (BDKRB2), Teneurin transmembrane protein 2 (TENM2), transforming growth factor beta 2 (TGFB2), and solute carrier family 2 member 13 (SLC2A13) on the risk of ATDILI.The subjects comprised 746 Chinese tuberculosis (TB) patients. Custom-by-design 2x48-Plex SNPscanTM kit was employed to genotype 28 selected SNPs. The associations of SNPs with ATDILI risk and clinical phenotypes were analyzed according to the distributions of allelic and genotypic frequencies and different genetic models. The odds ratio (OR) with corresponding 95% confidence interval (CI) was calculated.Among subjects with successfully genotyped, 107 participants suffered from ATDILI during follow-up. In BDKRB2, patients with rs79280755 G allele or rs117806152 C allele were more vulnerable to ATDILI (PBonferronicorrection = .002 and .03, respectively). Rs79280755 increased the risk of ATDILI significantly whether in additive (OR = 3.218, 95% CI: 1.686-6.139, PBonferroni correction = .003) or dominant model (PBonferroni correction = .003), as well as rs117806152 (Additive model: PBonferroni correction = .05; dominant model: PBonferroni correction = .03). For TENM2, rs80003210 G allele contributed to the decreased risk of ATDILI (PBonferroni correction = .02), while rs2617972 A allele conferred susceptibility to ATDILI (PBonferroni correction = .01). Regarding rs2617972, significant findings were also observed in both additive (OR = 3.203, 95% CI: 1.487-6.896, PBonferroni correction = .02) and dominant model (PBonferroni correction = .02). Moreover, rs79280755 and rs117806152 in BDKRB2 significantly affected some laboratory indicators. However, no meaningful SNPs were observed in TGFB2 and SLC2A13.Our study revealed that both BDKRB2 and TENM2 genetic polymorphisms were interrogated in relation to ATDILI susceptibility and some laboratory indicators in the Western Chinese Han population, shedding a new light on exploring novel biomarkers and targets for ATDILI.


Assuntos
Antituberculosos/efeitos adversos , Sinalização do Cálcio/genética , Doença Hepática Induzida por Substâncias e Drogas/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Receptor B2 da Bradicinina/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Proteínas Facilitadoras de Transporte de Glucose/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Fator de Crescimento Transformador beta2/genética
6.
Medicine (Baltimore) ; 98(44): e17854, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689877

RESUMO

Breast cancer is the most common diagnosed malignancy in women. This study genotyped blood samples from 236 Han Chinese women with breast cancer and 128 healthy controls for single nucleotide polymorphisms (SNPs) rs2977537, rs2929970, rs2929973, rs2977530, and rs62514004, to determine whether these WNT1-inducible signaling pathway protein 1 (WISP-1) genetic polymorphisms increase the risk of developing breast cancer. Compared with wild-type (AA) carriers, those carrying the WISP1 rs62514004 AG or AG + GG genetic variants had a greater risk of developing breast cancer. In an evaluation of the association between clinicopathological aspects and the WISP1 SNP rs62514004 in the breast cancer cohort, patients with the GG genotype were less likely than those with the AA genotype to develop stage III/IV disease. Patients carrying the WISP1 rs2929973 GG + TT variant were almost twice as likely as those carrying the GT genotype to have estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors, while those with the WISP1 rs62514004 AG + GG genetic variants were around twice as likely as those with the AA genotype to have HER2-positive tumors. This study details risk associations between WISP1 SNPs and breast cancer susceptibility in women of Han Chinese ethnicity.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/genética , Proteínas de Sinalização Intercelular CCN/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Pessoa de Meia-Idade , Receptor ErbB-2/análise , Receptores Estrogênicos/análise , Receptores de Progesterona/análise , Fatores de Risco , Transdução de Sinais
7.
Medicine (Baltimore) ; 98(44): e17867, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689880

RESUMO

Glycogen storage disease (GSD) type IX, characterized by liver enlargement and elevated aminotransferase levels, is the most frequent type of GSD. The global incidence of GSD type IXa is only about 1/100,000 individuals. Case reports of GSD type IX are rare in China. We present the first case report of GSD type IXa in Northeast China caused by mutation of PHKA2.An 11-year-old boy was referred to our hospital because of liver enlargement with consistently elevated transaminase levels over 6 months.Histopathological results following an ultrasound-guided liver biopsy confirmed a diagnosis of GSD. Further genetic testing showed that the patient had GSD type IXa caused by the c.133C>T mutation in PHAK2.We placed the patient on a high-protein and high-starch diet and provided hepatoprotective and supportive therapy.The patient's transaminase levels decreased significantly and were nearly normal at 10-month follow-up.This is the first reported case of GSD type IXa in Northeast China. We hope that the detailed and complete report of this case will provide a reference for the diagnosis of liver enlargement of unknown etiology in future clinical practice.


Assuntos
Carcinoma Hepatocelular/virologia , Hepatite B Crônica/genética , Interleucinas/genética , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Polimorfismo de Nucleotídeo Único , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Grupo com Ancestrais do Continente Asiático/genética , Carcinoma Hepatocelular/genética , Estudos de Casos e Controles , Progressão da Doença , Feminino , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Estudos Retrospectivos , Fumar/efeitos adversos
8.
Medicine (Baltimore) ; 98(41): e17487, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593112

RESUMO

To analyze the association between glutathione S-transferases polymorphisms and the risk of cervical lesions.Case-control studies focusing on the association between glutathione S-transferase polymorphisms and the risk of cervical lesions were collected from the PubMed, Web of Science, Cochrane Library, Embase, Medline, CNKI, VIP and Wanfang databases from inception to August 2018. Pooled odds ratios and 95% confidence intervals were employed to evaluate the strength of the association. Subgroup analysis and sensitivity analysis were used to test the potential discrepancy and robustness, respectively.A total of 30 studies comprising 3961 patients and 4726 healthy controls satisfied the inclusion criteria. Of these, 6 studies contained information about GSTP1, 27 studies contained information about GSTM1, and 22 studies contained information about GSTT1. Our results supported that there was no statistical association between GSTP1 polymorphism and the risk of cervical lesions (odds ratio [OR] = 1.08, P = .40). The GSTM1 null variant showed increased susceptibility to cervical lesions (OR = 1.45, P < .001). Subgroup analysis revealed that the GSTM1 null variant caused cervical lesions among HPV infection cases (OR = 1.69, P = .02) and among the Chinese and Indian populations (OR = 2.24 and OR = 1.87, respectively, P < .001). The GSTT1 null variant increased the risk of cervical lesions in smokers (OR = 1.52, P = .03). The GSTT1 null genotype was also related to high-grade intraepithelial neoplasia (HSIL) and cervical cancer risk (OR = 1.30 and OR = 1.78, respectively, P < .05).The GSTM1 null variant caused cervical lesions, especially among HPV infection cases and among the Chinese and Indian populations. The GSTT1 null variant increased the risk of cervical lesions in smokers and was also related to HISL and cervical cancer risk.


Assuntos
Neoplasia Intraepitelial Cervical/genética , Predisposição Genética para Doença/genética , Glutationa Transferase/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias do Colo do Útero/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Neoplasia Intraepitelial Cervical/virologia , China , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genótipo , Glutationa S-Transferase pi/genética , Humanos , Índia , Pessoa de Meia-Idade , Razão de Chances , Infecções por Papillomavirus/genética , Fatores de Risco , Neoplasias do Colo do Útero/virologia
9.
Zhonghua Er Ke Za Zhi ; 57(10): 780-785, 2019 Oct 02.
Artigo em Chinês | MEDLINE | ID: mdl-31594065

RESUMO

Objective: To summarize the clinical and genetic characteristics of focal epilepsy in children caused by GATOR1 complex gene variation. Methods: The clinical data, gene variation and treatment outcome of 12 children with focal epilepsy caused by GATOR1 complex gene variation admitted to Beijing Children's Hospital Affiliated to Capital Medical University from June 2016 to October 2018 were retrospectively analyzed. Results: There were 7 males and 5 females in 12 cases. The epilepsy onset age was 5.5 (3.0, 12.0) months, and from 11 days to 16 months of age. The epileptic seizure types were all focal motor seizures, and one case combined with epileptic spasms. The frequency of seizures in all patients was more than one time per day. Seven cases had frontal lobe epilepsy and two cases had lateral temporal lobe epilepsy. One case had a family history of febrile seizures and two had a family history of suspicious epilepsy. Epileptic form discharges were observed in 9 patients during the interictal phase by electroencephalograms (EEG), and all of them were focal discharges. Eight cases had clinical seizures detected by EEG, in 4 of whom the seizures were originated in frontal region. There were no abnormalities in brain magnetic resonance imaging in 11 cases whereas 1 case had malformation of cortical development of left frontal lobe. Eight patients had DEPDC5 gene variation, one had NPRL2 gene variation, three had NPRL3 gene variation. One case had de novo variation and the other 11 had hereditary variation. There were 11 types of gene variation, including 5 nonsense variations, 3 missense variations, 2 frame shift variations and 1 in frame deletion variation. There was no clear relationship between the clinical phenotype and the genotype. During the follow-up period from 6 months to 2 years and 6 months, 6 cases had seizure control, 3 of them were controlled by oxcarbazepine. The other 6 cases had drug-refractory epilepsy, 2 of them failed with vagus nerve stimulation and ketogenic dietary therapy as well, meanwhile combined with mental retardation. Conclusions: GATOR1 complex gene variation can lead to genetic focal epilepsy, which usually has early onset with frequent seizures. Most of the patients have focal epileptic form discharges on EEG, and there is usually no structural lesion in brain imaging. Most of the patients have hereditary loss-of-function variations. Approximately half of cases are drug-resistant epilepsy.


Assuntos
Epilepsias Parciais/genética , Proteínas Ativadoras de GTPase/genética , Proteínas Repressoras/genética , Proteínas Supressoras de Tumor/genética , Grupo com Ancestrais do Continente Asiático/genética , Eletroencefalografia , Epilepsias Parciais/diagnóstico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Convulsões/complicações , Convulsões/genética
10.
Zhonghua Jie He He Hu Xi Za Zhi ; 42(10): 760-764, 2019 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-31594110

RESUMO

Objective: To explore the difference of mRNA, protein expression levels and the indexes of peripheral blood antioxidant capacity in peripheral blood lymphocytes of different EPHX1 genotypes in chronic obstructive pulmonary disease(COPD). Methods: A case-control study was conducted to collect peripheral blood samples of 220 stable chronic COPD patients with smoking history and 230 healthy smokers (control group) from October 2016 to February 2018 in the First Affiliated Hospital of Kunming Medical University, and the genetic testing was carried out according to the operation instructions of BigDye Terminator v1.1 DNA Sequencing Kit. Based on their EPHX1 exon 3 and exon 4 polymorphism status, the EPHX1 was classified into 4 groups, i. e., normal activity, slow activity, extremely slow activity and fast activity. Then COPD patients were allocated to either a slow activity group (slow and very slow activity) or a fast activity group (normal and fast activity) according to EPHX1 genotype and gene activity. The expression of EPHX1 mRNA and protein in peripheral blood lymphocytes were detected by qRT-PCR and Western blot, and indexes of serum antioxidant capacity was detected by corresponding kits. Results: (1)The 2(-ΔΔCt) of the control group was 1.000, and the 2(-ΔΔCt) of the COPD group was 1.052±0.023. There was no significant difference in the level of EPHX1 mRNA expression between the two groups (t=1.992 P=0.865). The level of EPHX1 mRNA expression in the slow activity group was not different significantly compared to that in the fast-active group (1.053±0.023 vs 1.048±0.021, t=1.133, P=0.260). (2)The level of EPHX1 protein expression by Western blot analysis showed that the EHPX1/GAPDH gray ratio was not different significantly between the COPD group and the control group (0.613±0.089 vs 0.602±0.075, t=0.805, P=0.422). The level of EPHX1 protein expression in the slow activity group was not significantly different compared to that in the fast activity group (0.606±0.088 vs 0.622±0.092, t=-0.786 P=0.434). (3)There were significant differences in indexes of antioxidant capacity between the control group and the COPD group (P<0.05). There were significant differences in indexes of antioxidant capacity between the slow activity group and the fast activity group of COPD patients (P<0.05). Conclusions: The different antioxidant capacity of COPD patients with different EPHX1 genotypes may be related to the polymorphism of EPHX1 gene affecting the activity of microsomal epoxidase, but not to the level of EPHX1 mRNA and protein expression.


Assuntos
Antioxidantes/metabolismo , Grupo com Ancestrais do Continente Asiático/genética , Epóxido Hidrolases/genética , Doença Pulmonar Obstrutiva Crônica/genética , Fumar/efeitos adversos , Adulto , Western Blotting , Estudos de Casos e Controles , China/epidemiologia , Epóxido Hidrolases/metabolismo , Predisposição Genética para Doença/genética , Genótipo , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/metabolismo , Humanos , Pessoa de Meia-Idade , Polimorfismo Genético , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Fumar/epidemiologia
11.
Anticancer Res ; 39(10): 5375-5380, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570432

RESUMO

BACKGROUND/AIM: Matrix metalloproteinases-11 (MMP-11) overexpression has been reported in various types of cancer including lung cancer. We aimed to examine the contribution of MMP-11 genotypes to lung cancer risk. MATERIALS AND METHODS: In this case-control study, the MMP-11 rs738791, rs2267029, rs738792 and rs28382575 genotypes were determined among 358 lung cancer patients and 716 age- and gender-matched healthy control Taiwanese. RESULTS: The percentages of rs738791 CT and TT were 50.6% and 9.2% in the case group, slightly higher than 48.5% and 8.1% in the control group (p for trend=0.5638). The allelic analysis showed that the rs738791 T allele did not confer lung cancer risk compared with the C allele. Similarly, there was no association between rs2267029, rs738792 or rs28382575 and lung cancer risk. There was no joint effect of MMP-11 genotypes among ever smokers or non-smokers. CONCLUSION: The genotypes of MMP-11 play a minor role in determining lung cancer risk in Taiwan.


Assuntos
Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Metaloproteinase 11 da Matriz/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taiwan
12.
Niger J Clin Pract ; 22(10): 1319-1323, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31607718

RESUMO

Background: Morphine is a common analgesic often used to manage chronic pain, especially for patients with pain due to malignancies. Since UGT2B7 plays an important role in the metabolism of morphine, UGT2B7 gene mutation may influence the efficacy of morphine in patients with cancer being treated by this medication. Aims: The aim of this study is to investigate the relationship between the polymorphisms of UGT2B7 and the efficacy of morphine treatment on cancer pain among the Chinese Han population. Materials and Methods: A total of 120 patients with cancer pain were enrolled in this study. Morphine was administrated through patient-controlled analgesia infusion pump, and the visual analog score (VAS) was used for pain assessment at 0.5, 4, 6, 12, 24, 48, and 72-h post morphine treatment, respectively. The plasma concentration of morphine and genetic polymorphism of UGT2B7 C802T and G221T was analyzed, respectively. Results: The frequencies of UGT2B7 C802T were CC: 13.33%, CT: 45% and TT: 41.67%, and the frequencies of UGT2B7 G221T were GG: 76.67%, GT: 22.5% and TT: 0.83%. Moreover, the VAS score of patients with either C802T CT or TT was significantly higher than that in patients with C802T CC. However, no difference of VAS scores was observed between patients carrying G221T GG and patients carrying G221T GT. The plasma concentration of morphine for patients with the C802T CC was significantly lower than that in patients carrying C802T CT or TT, while there was no significant difference in the level of morphine between patients with G221T GG and G221T GT. Conclusion: The polymorphism of UGT2B7 C802T, but not UGT2B7 G221T, has been associated with the efficacy of morphine treatment on cancer pain among Chinese Han population.


Assuntos
Analgésicos Opioides/sangue , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Dor do Câncer/tratamento farmacológico , Glucuronosiltransferase/genética , Morfina/sangue , Neoplasias/sangue , Polimorfismo Genético/genética , Adulto , Analgesia Controlada pelo Paciente , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/uso terapêutico , Grupo com Ancestrais do Continente Asiático/genética , Dor do Câncer/genética , Feminino , Genótipo , Humanos , Bombas de Infusão , Masculino , Pessoa de Meia-Idade , Morfina/administração & dosagem , Morfina/uso terapêutico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/genética , Medição da Dor , Escala Visual Analógica
13.
Chem Biol Interact ; 313: 108840, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31585114

RESUMO

BACKGROUND AND OBJECTIVES: Clonidine has been clinically used to treat Tourette's syndrome for decades. There was research finding that clonidine possessed the best risk-benefit ratio, especially for patients associated with attention deficit hyperactivity disorder. CYP2D6 is a significant member of Cytochrome P450 enzymes. The genetic polymorphisms of CYP2D6 greatly affect the clinical effects of drugs even lead to side effects and medical malpractice. Our goal is to research the effect of CYP2D6 genetic polymorphism on the metabolism of clonidine and evaluate the functions of 22 CYP2D6 allelic variants in vitro, which were discovered in Chinese Han population recently. METHODS: This study was carried out through a mature incubation system. The wild-type CYP2D6*1 and 24 variants (CYP2D6*2, CYP2D6*10 and 22 novel CYP2D6 variants) were expressed in insect cells, and the catalytic activity of all the variants were assessed by substrate clonidine. Metabolite 4-OH clonidine was accurately detected via ultra-performance liquid-chromatography tandem mass spectrometry to evaluate the effect of CYP2D6 genetic polymorphism on the clonidine. RESULT: Among the 22 novel CYP2D6 variants, the intrinsic clearance (Vmax/Km) of 21 variants were significantly decreased (from 1.53% to 83.25%) compared to the wild-type. In particular, the following seven variants (CYP2D6* 2, CYP2D6* 10, CYP2D6* 93, CYP2D6* 95, E215K, V327 M and R497C) attract more attention, of which the intrinsic clearance decreased more than 70% compared to the wild-type. Because the variants with significantly reduced intrinsic clearance are more likely to cause adverse reactions than the variants with increased or little changed intrinsic clearance. In addition, the related pharmacokinetic parameters of CYP2D6*92 and CYP2D6*96 could not be acquired for the defect of CYP2D6 nucleotide. CONCLUSION: We comprehensively evaluated the effect of 22 novel CYP2D6 variants on the metabolism of clonidine for the first time and hoped corresponding data provide a reference for metabolism of clonidine for further studies in vivo, and extend our understanding of the clinical drug toxicity or ineffectiveness by CYP2D6 genetic polymorphism.


Assuntos
Clonidina/farmacocinética , Citocromo P-450 CYP2D6/genética , Grupo com Ancestrais do Continente Asiático/genética , Clonidina/metabolismo , Citocromo P-450 CYP2D6/metabolismo , Humanos , Polimorfismo Genético
14.
Medicine (Baltimore) ; 98(40): e17113, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577700

RESUMO

BACKGROUND: Periodontitis is a common disease with an unclear pathological mechanism. No precise consensus has been reached to evaluate the association between the IL-10 rs1800872 (- 592, -590, -597 C>A) polymorphism and periodontal disease. Thus, we performed this meta-analysis to collect more evidence-based information. METHODS: Four online databases, PubMed, Embase, Web of Science, and China Biology Medicine disc (CBM), were searched in August 2018. An odds ratio (OR) with a 95% confidence interval (CI) was applied to evaluate the association of the rs1800872 with periodontitis susceptibility. RESULTS: Twenty three case-control studies with 2714 patients and 2373 healthy controls were evaluated. The overall analyses verified that the IL-10 rs1800872 polymorphism was significantly associated with an increased risk of periodontitis in the allelic model, homozygote model, dominant model, and recessive model (A vs C: OR = 1.28, 95%CI = 1.11-1.49, P = .00, I = 56.87%; AA vs CC: OR = 2.06, 95%CI = 1.32-3.23, P = .00, I = 73.3%; AA + AC vs CC: OR = 1.42, 95%CI = 1.03-1.96, P = .03, I = 76.2%; AA vs AC + CC: OR = 1.78, 95%CI = 1.26-2.56, P = .00, I = 76.7%). Moreover, the subgroup analysis based on ethnicity, periodontitis type, and smoking status showed significant differences. CONCLUSIONS: The results of our meta-analysis demonstrate that rs1800872 is associated with periodontitis susceptibility in Caucasians and Asians. Moreover, A allele, AA genotype, CC genotype may be closely associated with chronic periodontitis (CP), while A allele, AA genotype may be closely associated with aggressive periodontitis (AgP).


Assuntos
Interleucina-10/genética , Periodontite/etnologia , Periodontite/genética , Periodontite Agressiva/etnologia , Periodontite Agressiva/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China , Periodontite Crônica/etnologia , Periodontite Crônica/genética , Grupo com Ancestrais do Continente Europeu/genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Fumar/etnologia
15.
Medicine (Baltimore) ; 98(43): e17258, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651836

RESUMO

Increasing studies demonstrated that genetic susceptibility attributes to the development of gestational diabetes mellitus (GDM). The polymorphisms of the ß-3 adrenergic receptor(ß-3AR) gene have been found to be of great importance in bodyweight elevation and dyslipidaemias. We aimed to determine the influence of ß-3AR polymorphisms on the GDM risk. Thus, we performed a case-control study including 136 GDM cases and 138 controls to evaluate the relation between the rs201607471 and susceptibility to GDM. Likelihood ratios X analysis showed the distribution of the genotype frequency (rs201607471 in ß-3AR gene) was accorded with the Hardy-Weinberg genetic equilibrium. Although no significant association between rs201607471 alleles and GDM susceptibility (Chi-square test, P > .05), we observed that ß-3AR gene rs201607471 CT genotype was significantly prevalent in GDM (Chi-square test, P < .05). Moreover, we observed that ß-3AR gene rs201607471 C > T was significantly associated with an increased risk of GDM using the recessive model (CC vs CT/TT: P = .026) and the additive model (CC vs CT vs TT: P = .038). These data indicate that ß-3AR rs201607471 may be a helpful susceptibility marker for GDM in Chinese pregnant women.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Diabetes Gestacional/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores Adrenérgicos beta 3/genética , Adulto , Alelos , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , China , Feminino , Frequência do Gene , Genótipo , Humanos , Gravidez , Estudos Retrospectivos , Fatores de Risco
16.
Medicine (Baltimore) ; 98(43): e17432, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651846

RESUMO

BACKGROUND: Several studies have explored the prognostic value of stanniocalcin 2 (STC2) in various cancers, but obtained inconsistent results. Therefore, this meta-analysis was performed to determine the prognostic and clinicopathologic significance of STC2 in various cancers. METHODS: Eligible studies were identified by searching the online databases PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure up to March 2019. Hazard ratios (HRs) with 95% confidence intervals (CIs) and were calculated to clarify the correlation between STC2 expression and prognosis of different cancers. Odds ratios (ORs) with 95% CI were selected to appraise the correlation between STC2 with clinicopathologic characteristics of patients with cancer. RESULTS: A total of 16 eligible studies with 4074 patients with cancer were included in our meta-analysis. The results showed that high STC2 expression can predict poor overall survival (OS) for cancer (HR = 1.48, 95% CI: 1.15-1.90, P = .002). Subgroup analysis found that high STC2 expression was associated with worse OS in Asian (HR = 1.85, 95% CI: 1.35-2.55), the reported directly from articles group (HR = 1.39, 95% CI: 1.05-1.84), survival curves group (HR = 1.93, 95% CI: 1.36-2.74), and gastric cancer (HR = 1.43, 95% CI: 1.04-1.95). Furthermore, high STC2 expression was significantly related to advanced T stage (OR = 1.83, 95% CI: 1.17-2.86, P = .008), lymph node metastasis (OR = 2.29, 95% CI: 1.51-3.45, P < .001), lymphatic invasion (OR = 2.15, 95% CI: 1.53-3.02, P < .001), venous invasion (OR = 1.97, 95% CI: 1.30-2.99, P = .001), and more advanced clinical stage (OR = 2.36, 95% CI: 1.74-3.19, P < .001) CONCLUSION:: Elevated expression of STC2 suggested a poor prognosis in patients with cancer and may serve as a new tumor marker to monitor cancer development and progression.


Assuntos
Glicoproteínas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Neoplasias/sangue , Neoplasias/mortalidade , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Biomarcadores Tumorais/sangue , Feminino , Humanos , Metástase Linfática/genética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Estadiamento de Neoplasias , Neoplasias/patologia , Razão de Chances , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Gástricas/sangue , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia
17.
Medicine (Baltimore) ; 98(43): e17482, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651850

RESUMO

The aim of this study was to investigate the correlation between cluster of differentiation 86 (CD86) gene rs1129055 and rs2715267 single nucleotide polymorphisms and sepsis susceptibility.One hundred twenty-five sepsis patients and 120 healthy controls were enrolled in this case-control study. CD86 polymorphisms rs1129055 and rs2715267 were genotyped through polymerase chain reaction-restriction fragment length polymorphism approach. Chi-square test was used to analyze differences in genotype and allele frequencies of the 2 polymorphisms between case and control groups. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to present the association strength of the polymorphisms with sepsis susceptibility.AA genotype and A allele frequencies of CD86 rs1129055 were significantly lower in sepsis patients than in healthy controls (P < .05), revealing their significant associations with decreased disease susceptibility (OR = 0.351, 95% CI = 0.169-0.728; OR = 0.593, 95% CI = 0.415-0.847). Nevertheless, rs2715267 had no significant association with sepsis susceptibility (P > .05).AA genotype and A allele of CD86 polymorphism rs1129055 might be correlated with decreased sepsis susceptibility in Chinese Han population, but not rs2715267. Further study should be performed to verify our findings.


Assuntos
Antígenos CD/sangue , Antígeno B7-2/sangue , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Sepse/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Adulto Jovem
18.
Medicine (Baltimore) ; 98(43): e17578, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31651862

RESUMO

BACKGROUND: To evaluate the methylation levels of human telomerase reverse transcriptase (hTERT) promoter three CpG island (CGIs) regions and its prognostic impact in Chinese patients with acral and mucosal melanoma. METHODS: Bioinformatics software was used to analyze hTERT gene promoter. Fresh frozen tissues were taken from 14 patients with melanoma (6 acral melanoma and 8 mucosal melanoma) and 14 pigmented nevus as control subjects (14 acral pigmented nevus). Bisulfite sequencing PCR (BSP) combined TA clone sequencing was used to assess the methylation levels of hTERT promoter CGIs regions. The relative expression level of hTERT mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: CGIs-1 (-1392--1098 bp), CGIs-2 (-945--669 bp), and CGIs-3 (-445--48 bp) were selected for our study. Our results indicated that the methylation levels of hTERT promotor CGIs regions in melanoma were greater than pigmented nevus (CGIs-1: 69.3 ±â€Š18.7% vs 46.8 ±â€Š20.4%, t = 3.048 P = .005; CGIs-2: 73.8 ±â€Š14.7% vs 55.6 ±â€Š16.0%, t = 3.120 P = .004; CGIs-3: 5.8 ±â€Š2.2% vs 2.2 ±â€Š1.3%, t = 5.164 P < .001). The relative expression level of hTERT in melanoma was greater than in pigmented nevus (50.39 ±â€Š9.16 vs 26.10 ±â€Š7.25, t = 7.778, P < .001). Linear regression analysis showed that the methylation level of CGIs-2 in melanoma was positively correlated with the relative expression level of hTERT mRNA (R = .490, F = 13.478, P = .003). Combined with the analysis of clinicopathological features, the methylation level of CGIs-2 in melanoma with lymph node metastasis was greater than in melanoma without lymph node metastasis, and the methylation level of CGIs-2 increased with TNM staging. CONCLUSION: CGIs-2 methylation level was associated with the relative expression level of hTERT mRNA, lymph node metastasis and TNM staging, suggesting that CGIs-2 hypermethylation might be used to evaluate the prognosis in Chinese patients with acral and mucosal melanoma.


Assuntos
Ilhas de CpG/genética , Metilação de DNA/genética , Melanoma/genética , Proteína 2 de Ligação a Metil-CpG/metabolismo , Telomerase/metabolismo , Idoso , Grupo com Ancestrais do Continente Asiático/genética , China , Biologia Computacional , Feminino , Humanos , Modelos Lineares , Metástase Linfática , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , RNA Mensageiro/metabolismo
19.
Arq Bras Cir Dig ; 32(3): e1449, 2019.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31644669

RESUMO

INTRODUCTION: The matrix metalloproteinase-7 (MMP-7) gene -181A>G polymorphism has been reported to be associated with colorectal cancer (CRC) and gastric cancer (GC) susceptibility, yet the results of these previous results have been inconsistent or controversial. AIM: To elaborate a meta-analysis to assess the association of -181A>G polymorphism of MMP-7 with CRC and GC risk. METHODS: Published literature evaluating the association from PubMed, Web of Science, Google Scholar and other databases were retrieved up to April 25, 2018. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using random- or fixed-effects model. RESULTS: A total of 19 case-control studies, which included eleven studies on CRC (2,169 CRC cases and 2,346 controls) and eight studies on GC (1,545 GC cases and 2,366 controls) were identified. There was a significant association between MMP-7 -181A>G polymorphism and GC risk under the homozygote model (GG vs. AA: OR=1.672, 95% CI 1.161-2.409, p=0.006) and the recessive model (GG vs. GA+AA: OR=1.672, 95% CI 1.319-2.554, p=0.001), but not with CRC. By subgroup analysis based on ethnicity, an increased risk of CRC and GC was found only among Asians. CONCLUSIONS: This meta-analysis suggests that MMP-7 -181A>G polymorphisms is associated with GC risk, but not with CRC. However, our results clearly showed that the MMP-7 -181A>G polymorphism significantly increased the risk of CRC only in Asians.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Metaloproteinase 7 da Matriz/genética , Polimorfismo Genético/genética , Neoplasias Gástricas/genética , Grupo com Ancestrais do Continente Asiático/genética , Predisposição Genética para Doença/etnologia , Humanos , Razão de Chances , Fatores de Risco
20.
DNA Cell Biol ; 38(11): 1249-1256, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31553233

RESUMO

Transmembrane protein 39A (TMEM39A) gene polymorphisms have been related to various autoimmune diseases, but the relationship between TMEM39A polymorphisms and autoimmune thyroid disease (AITD) remains unknown. This study was aimed at investigating whether the polymorphisms of the TMEM39A were associated with AITD in the Chinese Han population. A case-control study was performed in a total of 906 AITD patients and 744 healthy controls. Four single nucleotide polymorphisms, including rs1132200, rs12492609, rs2282175, and rs7629750, in TMEM39A were examined by polymerase chain reaction-ligase detection reaction. We found that the allele T of rs12492609 in TMEM39A was associated with AITD and Hashimoto's thyroiditis (HT) (p = 0.023; p = 0.028 respectively). Compared with controls, the frequency of haplotype CCA in AITD patients was higher than that in controls (p = 0.036), but the frequency of haplotype CTA in AITD and HT patients was lower than that in controls (p = 0.046; p = 0.047 respectively). In addition, the frequency of allele A at rs7629750 in AITD patients with onset age ≤18 years old was higher than that in AITD patients with onset age ≥19 (p = 0.046). Further, there was an obvious difference in the genotype distributions of rs12492609 and rs7629750 between HT patients with hypothyroidism and those without hypothyroidism (p = 0.034 and p = 0.023, respectively). Our study first reveals that the polymorphisms of the TMEM39A gene are associated with the susceptibility to AITD, especially for early-onset AITD and HT with hypothyroidism.


Assuntos
Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Tireoidite Autoimune/genética , Adolescente , Adulto , Idade de Início , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Doença de Hashimoto/epidemiologia , Doença de Hashimoto/genética , Humanos , Hipotireoidismo/epidemiologia , Hipotireoidismo/genética , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Tireoidite Autoimune/epidemiologia , Adulto Jovem
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