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1.
Cancer Cell Int ; 21(1): 405, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34330284

RESUMO

BACKGROUND: WNT1-inducible signaling pathway protein 1 (WISP1) is a member of the CCN protein family and a downstream target of ß-catenin. Aberrant WISP1 expression may be involved in carcinogenesis. To date, no studies have investigated the association between single-nucleotide polymorphisms (SNPs) of WISP1 and gastric cancer. Therefore, we conducted this study to explore their relationship. METHODS: Polymerase chain reaction-restriction fragment length polymorphism assay was used to analyze three SNPs of WISP1 in 204 gastric cancer patients and 227 controls. RESULTS: Overall, we could not identify a significant association between WISP1 SNPs and gastric cancer risk. However, the subgroup analysis demonstrated that the presence of the rs7843546 T allele was associated with a significantly decreased risk of gastric cancer in those of Han Chinese ethnicity (CT vs. CC: OR = 0.33, 95%CI 0.14-0.78; TT vs. CC: OR = 0.29, 95%CI 0.11-0.76; CT + TT vs. CC: OR = 0.32, 95%CI 0.14-0.74). In addition, patients with the rs7843546 TT genotype display a 0.34-fold lower risk of developing stage I/II gastric cancer than those with the CC genotype Furthermore, individuals ≥ 50 years old who carried the rs10956697 AC genotype had a significantly decreased risk of gastric cancer (OR = 0.58, 95%CI 0.35-0.98). Smokers with the rs10956697 AC and AC + AA genotypes exhibited a 0.28-fold lower and 0.32-fold lower risk of gastric cancer, respectively. CONCLUSIONS: The WISP1 SNPs rs7843546 and rs10956697 were, for the first time, found to reduce susceptibility to gastric cancer in various subgroups of Guangxi Chinese.

2.
Cancer Cell Int ; 21(1): 157, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33685462

RESUMO

BACKGROUND: Uterine leiomyosarcoma (ULMS) is a malignant tumor found in the smooth muscle lining the walls of the uterus. Cancer stem cells (CSCs) are responsible for metastasis, drug resistance, and relapse of cancer, resulting in treatment failure. However, little is known about CSCs and their associated-markers in ULMS. We aimed to characterize and identify a subpopulation of CD133+ cancer stem-like cells derived from SK-UT-1 cell line. METHODS: SK-UT-1 cells were sphere-forming cultured in vitro. We also sorted the CD133+ cells derived from SK-UT-1 cell line by immunomagnetic beads. CD133+ subpopulation and apoptotic cells were detected by flow cytometry. Self-renewal and anchorage-independent growth capabilities were examined using sphere and colony formation assays. The tumorigenicity of the fourth-passage spheres and parental SK-UT-1 cells was used by mouse xenograft model in vivo. Cell proliferation ability and sensitivity to doxorubicin (DXR) were assessed by CCK-8 assay. Cell migration and invasion were tested by wound healing assay or Transwell migration and invasion assays. Expressions of CSC-related marker were analyzed by Western blotting. RESULTS: The fourth-passage spheres were defined as a CD133+ cell population, which was accompanied by increase of sphere and colony forming rate, migration and invasion abilities, as well as drug-resistant properties in vitro. Moreover, the fourth-passage spheres showed a stronger tumorigenic potential in vivo. CD133+ cell population sorted from SK-UT-1 line showed an increased ability in sphere and colony formation, proliferation, migration, invasion, resistance to apoptosis after treatment with doxorubicin (DXR) compared with CD133- cell population. The expression levels of CSCs-related markers (e.g., CD44, ALDH1,BMI1, and Nanog), were significantly elevated in CD133+ cells compared with those in CD133- cells. CONCLUSIONS: Collectively, our findings indicated that CD133 may be a significant marker for cancer stem-like cells, and it may be a potential therapeutic target for human ULMS.

3.
Cell Metab ; 31(6): 1068-1077.e3, 2020 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-32369736

RESUMO

Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.


Assuntos
Glicemia/análise , Infecções por Coronavirus/mortalidade , Diabetes Mellitus Tipo 2/sangue , Índice Glicêmico/fisiologia , Hiperglicemia/sangue , Pneumonia Viral/mortalidade , Idoso , Betacoronavirus/patogenicidade , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Diabetes Mellitus Tipo 2/complicações , Suscetibilidade a Doenças/patologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hiperglicemia/complicações , Hipoglicemiantes/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/complicações , Insuficiência de Múltiplos Órgãos/mortalidade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Estudos Retrospectivos , SARS-CoV-2
4.
Liver Int ; 40(6): 1327-1338, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32187823

RESUMO

BACKGROUND AND AIMS: Little is known about the mechanisms of IL-17 secreting T cells accumulation in HBV-transfected livers. Here, we investigated the role of the chemokines CCL17, CCL20 and CCL22 in this process. METHODS: Peripheral blood and liver tissues were obtained from 30 chronic hepatitis B (CHB) patients and 15 healthy volunteers and were evaluated by flow cytometric analysis and immunohistochemistry. Chemokine production by monocyte-derived dendritic cells (MoDCs) cocultured with HBV-transfected or untransfected Huh7 cells was measured by quantitative real-time PCR and enzyme-linked immunosorbent assay. The chemotactic activity of the culture supernatants was also tested. RESULTS: The proportions of IL-17 secreting CD4 (Th17) and CD8 (Tc17) T cells were both increased in liver and peripheral blood mononuclear cells of CHB patients compared to those in HVs. CHB patients showed higher intrahepatic levels of CCL17 mRNA, CCL22 mRNA, CCR6 mRNA and CCR4 mRNA than HVs. The expression of CCR6 and CCR4 on the surface of Th17 and Tc17 cells in CHB patients was also significantly higher than that in HVs. Significant correlations existed between the CCR4/CCR6 levels and both the alanine transaminase levels and HBV DNA loads. Contact between MoDCs and pBlue-HBV-transfected Huh7 cells induced the expression of CCL17 and CCL22 dependent on the dose of HBV DNA. However, CCL20 expression was lower in CHB patients than in HVs. Transwell experiments showed that upregulation of CCL17 and CCL22 enhanced the migration of IL-17 secreting T cells. CONCLUSIONS: Contact of HBV-transfected cells with MoDCs induces CCL17 and CCL22 chemokine production, which may favour the recruitment of Th17 and Tc17 cells to liver tissue in CHB. Our results reveal the mechanism of IL-17 secreting T cells recruitment to liver tissue and thus provide new immunotherapy targets for CHB patients.


Assuntos
Vírus da Hepatite B , Interleucina-17 , Quimiocina CCL17 , Quimiocina CCL22 , Humanos , Leucócitos Mononucleares , Células Th17
5.
Gene ; 688: 107-118, 2019 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-30529247

RESUMO

BACKGROUND: Several investigators have reported that complement receptor 1 (CR1) likely play a role in the pathogenesis of tumors, autoimmune and inflammatory diseases. However, the association of genetic polymorphisms of CR1 with risk of hepatitis B virus (HBV)-related liver disease remains unexplored. METHODS: In a case-control study of 399 HBV-related liver disease patients and 227 healthy controls, we genotyped two SNPs in CR1 (rs3811381 and rs2274567) and assessed their associations with risk of HBV-related liver disease. RESULTS: No significant differences were observed in the frequency distribution of genotypes or alleles between CR1 rs3811381 and rs2274567 polymorphisms in patients and controls. However, stratification analysis indicated that these two CR1 polymorphisms may contribute to the risk of HBV- hepatocellular carcinoma (HCC) and chronic hepatitis B (CHB) in subgroups of males, alcohol drinkers and nonsmokers. Further, our results showed that the rs3811381 polymorphism may contribute to HBV-HCC risk in subgroups of older and younger subjects, while the G allele, AG and the combined AG + GG genotypes of rs2274567 may be risk factors for HBV-HCC in younger subjects. In addition, our results indicated that subjects who carried the rs3811381 G allele and the rs2274567 AG genotype were at decreased risk of HBV- liver cirrhosis (LC) in subgroups of females. CONCLUSIONS: Our results support the hypothesis that the CR1 gene rs3811381 and rs2274567 polymorphisms may contribute to HBV-HCC and HBV-CHB risk, particularly in subgroups of males, alcohol drinkers, nonsmokers, while these two CR1 polymorphisms were found to associate with decreased risk of HBV-LC, particularly in females. Further validation of these results is warranted.


Assuntos
Predisposição Genética para Doença/genética , Hepatite B Crônica/genética , Hepatopatias/genética , Hepatopatias/virologia , Fígado/virologia , Polimorfismo de Nucleotídeo Único/genética , Receptores de Complemento 3b/genética , Adulto , Alelos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Vírus da Hepatite B/patogenicidade , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade
6.
Int J Rheum Dis ; 22(4): 608-613, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30338637

RESUMO

AIM: Caregivers of patients with rheumatoid arthritis (RA) often experience a sense of burden and depression. This study aimed to determine the degree of burden and depression on caregivers of RA patients and identify characteristics of both patients and caregivers that may contribute to that distress. METHODS: A convenience sample of 195 patients with RA and their caregivers completed a demographic questionnaire, Zarit Care Burden Scale, Center Depression Self Rating Scale, Health Assessment Questionnaire Disability Index, and the Short Form Health Survey. Univariate and multivariate regression analysis were used to evaluate contributing factors. RESULTS: Overall, caregivers' feelings of burden and depression were moderate, with 52 (26.7%) feeling depression and 156 (80%) feeling burdened. Caregivers with poorer health (OR = 4.393; 95% CI = 1.155-16.708; P = 0.030) and less education (OR = 6.458; 95% CI = 1.675-24.895; P = 0.007) experienced greater burdens than those with better health and more education. The greatest degree of stress occurred during the first 6 months of providing care and after 5 years of caregiving. CONCLUSIONS: Overall occurrence of depression among caregivers is low. Caregivers with poorer health, less education and closer relationship with the patient bear a heavier burden. Healthcare professionals should be aware of these potential problems and provide information and support to ensure the best quality of life for both RA patients and their caregivers.


Assuntos
Artrite Reumatoide/terapia , Cuidadores/psicologia , Efeitos Psicossociais da Doença , Depressão/psicologia , Estresse Psicológico/psicologia , Adaptação Psicológica , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/psicologia , China/epidemiologia , Depressão/diagnóstico , Depressão/epidemiologia , Escolaridade , Emoções , Feminino , Nível de Saúde , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Qualidade de Vida , Medição de Risco , Fatores de Risco , Estresse Psicológico/diagnóstico , Estresse Psicológico/epidemiologia , Inquéritos e Questionários , Fatores de Tempo , Adulto Jovem
7.
Rheumatol Int ; 37(4): 537-545, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28154898

RESUMO

The multidrug resistance 1 gene (MDR1) encodes for P-glycoprotein (P-gp), which plays a pathophysiological role in the development of autoimmune diseases, including systemic lupus erythematosus (SLE). Herein, we aimed to investigate the relationship between MDR1 gene polymorphisms and SLE susceptibility in the Chinese Guangxi population. The genotypes of rs1128503 and rs1045642 in MDR1 gene were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method in 283 SLE patients and 247 healthy controls from Guangxi. Direct sequencing method was used to verify the results. Binary logistic regression analyses adjusting for gender and age indicated that subjects carrying the rs1128503 T-allele and TT genotype were at increased risk of SLE when compared to carriers of the C allele and CC genotype, with adjusted ORs of 1.36 (95% CI 1.07-1.74; P = 0.014) and 1.77 (95% CI 1.08-2.88; P = 0.022), respectively. In addition, the risk allele T had a recessive effect (OR 1.49, 95% CI 1.04-2.14, P = 0.029). Subgroup analyses revealed effect modification by age for the presence of the rs1128503 T allele, yielding a significant positive association with SLE in older (≥40 years) subjects (T vs. C allele: OR 1.41, 95% CI 1.01-1.96; P = 0.041; TT vs. CC genotype: OR 1.74, 95% CI 1.07-2.79; P = 0.021). For the first time, we demonstrated that MDR1 rs1128503 polymorphisms were associated with SLE susceptibility in Chinese Guangxi population.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
Cancer Cell Int ; 17: 19, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28184178

RESUMO

BACKGROUND: To investigate the influence of polymorphisms in the receptor for advanced glycation end products (RAGE) gene and circulating soluble RAGE (sRAGE) levels on susceptibility to gastric cancer, and identify whether these polymorphisms were correlated with serum sRAGE levels. METHODS: We performed a hospital-based case-control study involving 200 gastric cancer patients and 207 cancer-free controls. Four well-characterized RAGE genetic polymorphisms, namely, rs1800624, rs1800625, rs184003, and rs2070600 were genotyped by PCR-RFLP. RESULTS: The rs2070600 AG genotype might play a predominant role in the development of gastric cancer (adjusted OR 1.62, 95% CI 1.03-2.58). In contrast, the rs184003 GT genotype represented significantly reduced risk for gastric cancer (adjusted OR 0.62, 95% CI 0.39-0.99). Subgroup analysis demonstrated that rs2070600 AG variant genotype enhanced the gastric cancer risk among nonsmokers (OR 1.71, 95% CI 1.01-2.91), nondrinkers (OR 1.75, 95% CI 1.03-2.97), and patients with tumor stage III (OR 2.00, 95% CI 1.13-3.56). The average sRAGE levels in the gastric cancer patients were significantly decreased compared with those of the healthy controls. Subjects carrying the rs2070600 AG genotype had a decreased ability to produce sRAGE. Subjects carrying the rs184003 T variant allele had an increased ability to sRAGE. CONCLUSIONS: These findings suggested that the variant genotypes of rs184003 and rs2070600 in the RAGE gene exhibit significant associations with gastric cancer risk and circulating sRAGE levels inverse change simultaneously, leading to a marked causal estimate between lowered sRAGE levels and increased gastric cancer risk.

9.
PLoS One ; 11(7): e0158241, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27384772

RESUMO

OBJECTIVE: Hypoxia-inducible factor-2 alpha (HIF-2a) plays a major role in the progression of disease, although the role of HIF-2α gene polymorphisms in hepatitis B virus (HBV)-related diseases remains elusive. The aim of this study is to determine whether HIF-2a rs13419896 and rs6715787 single-nucleotide polymorphisms (SNPs) are associated with susceptibility to chronic hepatitis B (CHB), liver cirrhosis (LC), or hepatocellular carcinoma (HCC). METHOD: A case-control study of 107 patients with CHB, 83 patients with LC, 234 patients with HCC, and 224 healthy control subjects was carried out, and the HIF-2a rs13419896 and rs6715787 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: No significant differences were observed in the genotype or allele frequency of two HIF-2a SNPs between the cases and controls (all p>0.05). However, in subgroup analysis by gender, the HIF-2a rs13419896 GA and AA genotypes were significantly associated with a risk of CHB (odds ratio [OR] = 3.565, 95% confidence interval [CI] = 1.123-11.314, p = 0.031 and OR = 12.506, 95% CI = 1.329-117.716, p = 0.027) in females, and the A allele of rs13419896 was associated with a risk of CHB (OR = 2.624, 95% CI = 1.244-5.537, p = 0.011) and LC (OR = 2.351, 95% CI = 1.002-5.518, p = 0.050) in females. The rs6715787 CG genotype polymorphism may contribute to a reduced risk of LC in the Guangxi Zhuang Chinese population (OR = 0.152, 95% CI = 0.028-0.807, p = 0.027), as determined via subgroup analysis by ethnicity. Moreover, binary logistic regression analyses that were adjusted by drinking status indicated that the AA genotype of rs13419896 may contribute to an increased risk of LC in the non-alcohol-drinking population (OR = 3.124, 95% CI = 1.091-8.947, p = 0.034). In haplotype analysis, GG haplotype was significantly associated with a reduced risk of LC (OR = 0.601, 95% CI = 0.419-0.862, p = 0.005). CONCLUSIONS: The HIF-2a rs13419896 polymorphism is associated with an increased risk of CHB and LC in the Guangxi Chinese population, especially in females and in the non-alcohol-drinking population, while the HIF-2a gene rs6715787 polymorphism is associated with a decreased risk of LC in the Guangxi Zhuang population.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Hepatite B Crônica/genética , Hepatopatias/genética , Polimorfismo de Nucleotídeo Único , Adulto , Consumo de Bebidas Alcoólicas , Alelos , Carcinoma Hepatocelular/etnologia , Carcinoma Hepatocelular/genética , Estudos de Casos e Controles , China , Feminino , Fibrose/etnologia , Fibrose/genética , Predisposição Genética para Doença , Genótipo , Haplótipos , Vírus da Hepatite B , Hepatite B Crônica/etnologia , Humanos , Hepatopatias/etnologia , Neoplasias Hepáticas/etnologia , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Fragmento de Restrição , Risco
10.
Tumour Biol ; 37(5): 6599-606, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26643892

RESUMO

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) plays a critical role in different signaling pathways, cell cycle progression and proliferation, and gene expression, and it has been found to overexpress in many tumor tissues. Recently, researchers have found that PIN1 gene polymorphisms may alter the function of protein and be associated with the risk of cancer. The present study analyzed three common polymorphisms in promoter regions (rs2233678 and rs2233679) and in exon2 (rs2233682) of the PIN1 gene in 254 patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and 235 healthy controls in a Guangxi study population to determine whether any relationship exists between the polymorphisms and the risk of HBV-related HCC. The results revealed that the rs2233679 TT genotype was associated with increased risk of HCC with HBV infection [odds ratio (OR) = 2.04, 95 % confidence interval (95 % CI) = 1.13-3.69, p = 0.019]. This association was stronger in men than in women (OR = 2.17, 95 % CI = 1.09-4.34, p = 0.028) as well as in men 50 years of age and older (OR = 3.91, 95 % CI = 1.29-11.80, p = 0.016); moreover, for alcohol drinkers, being a carrier of the PIN1 rs2233679 CT genotype had a moderately increased risk of HCC (OR = 3.98, 95 % CI = 1.02-15.57, p = 0.047). In contrast, people carrying the rs2233682 GA genotype and A alleles were 0.23 times more likely to develop HCC (OR = 0.23, 95 % CI = 0.06-0.87, p = 0.031 and OR = 0.23, 95 % CI = 0.06-0.87, p = 0.030). No such associations were found in the PIN1 rs2233678 polymorphisms between the HBV-related HCC cases and the controls. In addition, the haplotype GCA was found to be a high protection factor for HCC with HBV infection (OR = 0.14, 95 % CI = 0.03-0.62, p = 0.003). In conclusion, this study's findings suggest that the PIN1 rs2233679 TT genotype, the rs2233682GA genotype, and A alleles might be associated with the HBV-related HCC in a Guangxi study population.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/etiologia , Hepatite B/complicações , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Peptidilprolil Isomerase de Interação com NIMA/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , China/epidemiologia , Genótipo , Haplótipos , Hepatite B/epidemiologia , Hepatite B/virologia , Humanos , Pessoa de Meia-Idade , Razão de Chances , Vigilância da População , Estudos Retrospectivos , Fatores de Risco
11.
Int J Neurosci ; 126(3): 199-204, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25562627

RESUMO

Several molecular genetics studies have investigated the association of NQO1 C609T polymorphism with Alzheimer's disease (AD) susceptibility in Chinese populations; however, the findings are inconclusive. To investigate the association, we performed the present meta-analysis of 5 case-control studies (including 735 AD cases and 828 controls). We searched literature from PubMed, Embase, HuGNet and CNKI databases for eligible articles that evaluated the association between NQO1 C609T polymorphism and AD risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to evaluate the strength of the association. Overall, C609T polymorphism was significantly associated with an increased AD risk (homozygote: OR = 1.87, 95% CI = 1.39-2.51, P = 0.000; heterozygote: OR = 1.93, 95% CI = 1.22-3.06, P = 0.019; dominant: OR = 1.97, 95% CI = 1.25-3.12, P = 0.004). When stratified by source of control, significant results were observed in subjects of population-based (PB), whereas no increased risk was observed among the hospital-based (HB). When stratified by APOEϵ4 carrier status, no effect of the NQO1 C609T polymorphism was seen in subjects of APOEϵ4 carriers and APOEϵ4 non-carriers. In conclusion, our results showed that NQO1 C609T polymorphism increases the risk of AD in Chinese populations. Larger studies with different ethnic populations are required to validate our findings.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença , NAD(P)H Desidrogenase (Quinona)/genética , Polimorfismo de Nucleotídeo Único , Apolipoproteína E4/genética , China , Humanos
12.
Clin Res Hepatol Gastroenterol ; 40(3): 288-296, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26546176

RESUMO

BACKGROUND: Interleukin (IL)-17 has been shown to play an important role in tissue inflammation and in the pathogenesis of immune-related liver damage. Genetic variations in IL-17 gene may be associated with the development of hepatitis B virus (HBV) infection. However, literature is scanty regarding their association. METHODS: We conducted a case-control study including 433 subjects (171 healthy controls, 130 patients with chronic hepatitis B [CHB]; and 132 patients with HBV-related liver cirrhosis [HBV-LC] to assess the association between IL-17A rs4711998, IL-17A rs2275913 and IL-17F rs763780 polymorphisms and risk of CHB and HBV-LC. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. RESULTS: Our results revealed a statistically significant association between IL-17A rs4711998 G allele and increased risk of HBV-LC risk (OR=1.541, 95% CI 1.057-2.246, P=0.025). Subjects carrying the IL-17A rs4711998 AG genotype were 1.75 times more likely to develop HBV-LC (OR=1.757, 95% CI 1.096-2.817, P=0.026). Stratification analysis indicated that IL-17A rs4711998 G allele and AG genotype enhanced the risk of HBV-LC development among men and older age (≥50years) subject groups. In addition, we found that GCT haplotype also might be a risk factor for HBV-LC (OR=2.448, 95% CI 1.137-5.271, P=0.019). Furthermore, no significant association between IL-17A rs2275913 and IL-17F rs763780 polymorphisms and CHB, HBV-LC risk was observed (P>0.05). CONCLUSION: Our data provide the first evidence that the IL-17A rs4711998 genetic variant may contribute to HBV-LC susceptibility in a Chinese population.


Assuntos
Predisposição Genética para Doença , Hepatite B Crônica/epidemiologia , Interleucina-17/genética , Polimorfismo Genético , /genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Genótipo , Vírus da Hepatite B , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade
13.
Medicine (Baltimore) ; 94(48): e2179, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26632904

RESUMO

Paraoxonase 1 (PON1), a liver-induced glycoprotein enzyme responsible for antioxidant defense against reactive oxygen species and anti-inflammatory, has been linked to various cancers. The objective of this study was to explore the association of PON1 rs662 and rs705382 with the risk of chronic hepatitis B (CHB), hepatitis B virus-related liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in patients living in the Guangxi region of southern China. The PON1 rs662 and rs705382 single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 99 CHB patients, 84 LC patients, 258 HCC patients, and 221 healthy controls.Significant associations with CHB risk were observed for the rs705382 SNP after adjusting for sex, age, ethnicity, smoking, alcohol consumption, and body mass index. When stratified by sex and age, this positive association was significantly strengthened among men and individuals over 40 years old. Moreover, a decreased risk of LC was associated with the rs705382 CG and the combined GG + CG genotypes among women, with borderline statistical significance. In haplotype analyses, the haplotype GA was associated with a 1.68-fold increase in the risk of HCC.Our results showed that the PON1 rs705382 SNP might be a risk factor for CHB in Guangxi populations.


Assuntos
Arildialquilfosfatase/genética , Carcinoma Hepatocelular/genética , Hepatite B Crônica/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Adulto , Carcinoma Hepatocelular/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Genótipo , Haplótipos , Hepatite B Crônica/epidemiologia , Humanos , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único
14.
Asian Pac J Cancer Prev ; 16(14): 6019-26, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26320490

RESUMO

BACKGROUND: The aim of this study was to assess the relationship between IL-18 gene polymorphisms and HBV-related diseases and whether these polymorphisms influence its expression in the Guangxi Zhuang population. MATERIALS AND METHODS: We enrolled 129 chronic HBV infected (CHB) patients, 86 HBV-related liver cirrhosis (LC) patients and 160 healthy controls in our study. Polymerase chain reaction-restriction fragment length polymorphism methods were used to detect IL-18 gene -607C/A, -137G/C polymorphisms, and an ELISA kit was employed to determine serum IL-18 levels. RESULTS: No correlation was found between the -607C/A polymorphism and risk of HBV-related disease. For the -137G/C polymorphism, the GC genotype and C allele were associated with a significantly lower risk of CHB (95%CI: 0.32-0.95, p=0.034 and 95%CI: 0.35-0.91, p=0.018) and HBV-related LC (95%CI: 0.24-0.89, p=0.022 and 95%CI: 0.28-0.90, p=0.021). A similar decreased risk was also found with the A-607C-137 haplotype. With respect to IL-18 expression, it was significantly lower in both patient groups, but no association was noted between the two polymorphisms in the IL-18 gene and its expression. CONCLUSIONS: Our study indicated that the -137C allele in the IL-18 gene may be a protective factor for HBV-related disease, and serum IL-18 level may be inversely associated with CHB and HBV-related LC.


Assuntos
Biomarcadores/análise , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/complicações , Interleucina-18/sangue , Interleucina-18/genética , Cirrose Hepática/etiologia , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Adulto , Estudos de Casos e Controles , China/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Haplótipos , Hepatite B Crônica/sangue , Hepatite B Crônica/genética , Hepatite B Crônica/virologia , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prognóstico , Estudos Retrospectivos
15.
Cancer Cell Int ; 15: 72, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26213495

RESUMO

BACKGROUND: Interleukin (IL)-18 gene polymorphisms have been found to play multiple roles in various diseases. However, studies focused on its involvement in hepatocellular carcinoma (HCC) remains controversial, and no much study has taken IL-18 serum levels into consideration. This study investigates the association between IL-18 polymorphisms and risk of hepatitis B virus-related HCC and their impact on serum IL-18 serum levels. METHODS: A total of 153 patients and 165 healthy controls were enrolled in this study. Polymorphisms at positions -607C/A and -137G/C in the IL-18 gene were determined using the polymerase chain reaction-restriction fragment length polymorphism method. Serum IL-18 levels were determined with an ELISA kit. RESULTS: No relationship was found between the -607C/A polymorphism and an individual's susceptibility to HCC. For the -137G/C polymorphism, the GC genotype and C allele were found to be significantly associated with decreased HCC risk (OR 0.506, 95% CI 0.290-0.882, P = 0.016 and OR 0.520, 95% CI 0.332-0.814, P = 0.004, respectively). The A(-607)C(-137) haplotype was also associated with a significant decreased risk of HCC (OR 0.495, 95% CI 0.294-0.834, P = 0.007). Serum IL-18 levels were found to be significantly lower in HCC patients compared to the control group in both the overall population and subjects with the different SNPs. Further, no association was found between serum IL-18 levels and the different genotypes within the same SNP. CONCLUSION: These findings suggest that the -137G/C SNP in IL-18 may be a protective factor against HCC. Nevertheless, none of the studied SNPs was associated with the expression of IL-18.

16.
PLoS One ; 10(5): e0123442, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25954818

RESUMO

BACKGROUND: Interleukin-16 (IL-16), a pleiotropic cytokine, plays a fundamental role in inflammatory diseases. This study investigates the association between IL-16 polymorphisms and the risk of knee osteoarthritis (OA) in a Chinese population. METHODS: The IL-16 rs11556218, rs4072111, and rs4778889 polymorphisms were determined in 150 knee OA cases and 147 healthy controls through polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The results suggested that the variants in IL-16 gene rs11556218 site were associated with a decreased knee OA risk after adjusting for age, sex, BMI, and smoking and drinking status (TG vs. TT: OR, 0.69; 95% CI, 0.53-0.89; P = 0.006; GG vs. TT: OR, 0.64; 95% CI, 0.45-0.90; P = 0.042; dominant model: OR, 0.68; 95% CI, 0.29-0.87; P = 0.002; G vs. T allele: OR, 0.77; 95% CI, 0.66-0.90; P = 0.003). Similarly, subjects bearing the rs4072111 variant genotypes and alleles also had a lower susceptibility to knee OA compared with those bearing the wild-type (CT vs. CC: OR, 0.66; 95% CI, 0.53-0.83; P = 0.002; TT vs. CC: OR, 0.57; 95% CI, 0.40-0.82; P = 0.027; dominant model: OR, 0.65; 95%, CI 0.52-0.80; P <0.001; T vs. C allele: OR, 0.69; 95% CI, 0.58-0.81; P <0.001). Further, the C allele and the combined genotype (CC+CT) of rs4778889 were associated with a slightly decreased risk of knee OA. In addition, we found two high-risk haplotypes: TTT (OR, 3.70) and GCC (OR, 6.22). Finally, serum IL-16 levels of knee OA patients were significantly higher than those of controls (P = 0.001). CONCLUSIONS: Despite the small sample size, this is the first study suggesting IL-16 gene polymorphisms to be associated with the risk of knee OA.


Assuntos
Interleucina-16/genética , Osteoartrite do Joelho/genética , Polimorfismo de Fragmento de Restrição , Idoso , Alelos , Estudos de Casos e Controles , China/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Interleucina-16/sangue , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/epidemiologia , Polimorfismo de Nucleotídeo Único , Risco
17.
Medicine (Baltimore) ; 94(13): e702, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25837767

RESUMO

Reactive oxygen species (ROS) play critical roles in hepatocarcinogenesis. The catalase (CAT) enzyme is involved in the repair of ROS. Therefore, we investigate the association between CAT gene polymorphisms and the risk of hepatocellular carcinoma (HCC). A total of 715 subjects were divided into 4 groups: 111 chronic hepatitis B (CHB) patients, 90 hepatitis B virus (HBV)-related liver cirrhosis (LC) patients, 266 HBV-HCC patients, and 248 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect CAT gene rs1001179, rs769217, and rs7943316 polymorphisms. Binary logistic regression analyses adjusting for sex, age, ethnicity, smoking and alcohol consumption, and body mass index suggested that subjects carrying the rs769217 T allele were at marginally increased risk of CHB, LC, and HCC, with adjusted odds ratios (ORs) of 1.51 (95% confidence interval [CI] = 1.04-2.20, P = 0.029), 1.48 (95% CI = 1.03-2.14, P = 0.035), and 1.51 (95% CI = 1.14-1.98, P = 0.004), respectively. Similarly, those individuals carrying the rs769217 TT genotype had a moderately increased risk of CHB, LC, and HCC, with adjusted ORs of 2.11 (95% CI = 1.05-4.22, P = 0.035), 2.00 (95% CI, 1.01-3.95, P = 0.047), and 1.93 (95% CI = 1.14-3.28, P = 0.015), respectively. Moreover, subjects carrying the rs769217 CT genotype and at least 1 copy of the T allele (dominant model) were 1.78 times and 1.83 times more likely to develop HCC, respectively (OR = 1.78, 95% CI = 1.16-2.73, P = 0.009 and OR = 1.83, 95% CI = 1.23-2.71, P = 0.003). This association between CAT rs769217 T alleles and HCC risk is significantly strengthened among men, nonsmokers, nondrinkers, and among individuals <50 years of age. Furthermore, we found 1 high-risk haplotype GTA for CHB (OR = 1.45, 95% CI = 1.05-2.01) and 1 protective haplotype GCA for HCC risk (OR = 0.67, 95% CI = 0.52-0.87). We did not found any significant difference in CAT rs1001179 and rs7943316 polymorphisms between controls and cases. Our findings suggest that the CAT rs769217 T allele is associated with increased risk of CHB, HBV-LC, and HBV-HCC in Guangxi population.


Assuntos
Carcinoma Hepatocelular/genética , Catalase/genética , Hepatite B Crônica/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Adulto , Fatores Etários , Consumo de Bebidas Alcoólicas/epidemiologia , Carcinoma Hepatocelular/epidemiologia , China/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Hepatite B Crônica/epidemiologia , Humanos , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Fatores Sexuais , Fumar/epidemiologia
18.
Gene ; 564(1): 96-100, 2015 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-25824382

RESUMO

BACKGROUND: Our recent study demonstrated a significant association between HIF-1α polymorphisms and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Since chronic hepatitis B (CHB), liver cirrhosis (LC), and HCC are progressive stages of chronic HBV infection, the aim of this study is to further determine if HIF-1α polymorphisms are associated with CHB and HBV-related LC. METHODS: Two HIF-1α polymorphisms (rs11549465 and rs115494657) were examined in 173 healthy controls, 153 patients with CHB, and 132 patients with HBV-related LC, using the polymerase chain reaction-restriction fragment length polymorphism method. DNA sequencing was also used to validate the genotype results. RESULTS: There were no significant differences regarding the HIF-1α rs11549465 and rs115494657 polymorphisms between the patient groups and the healthy controls, no matter the genotypes, alleles, or haplotypes. To exclude the potential influence of HBV infection in the association between HIF-1a and HBV-related LC, a comparison between the LC patients and HBV infected patients was also conducted, but a similar insignificant result was found. CONCLUSIONS: Our data suggest that the HIF-1α gene polymorphisms might not contribute to the development of CHB and HBV-related LC in a Chinese population.


Assuntos
Hepatite B Crônica/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Cirrose Hepática/virologia , Adulto , Sequência de Bases , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Risco
19.
AIDS Res Hum Retroviruses ; 31(5): 525-30, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25611551

RESUMO

Previous studies performed in Kenya have suggested that the C868T single nucleotide polymorphism (SNP) in CD4 increases the risk of HIV-1 acquisition; however, no relevant study has been conducted in China. To evaluate the influence of this SNP on risk of HIV-1 infection in a Chinese population, the CD4 genotype was determined by DNA sequencing in 101 HIV-1 patients and 102 healthy controls. No significant differences in the genotype and allele distributions of this polymorphism were observed among the patient and control groups. Additionally, binary logistic regression analyses adjusted by age and gender revealed that the C868T polymorphism was not associated with risk of HIV-1 infection. Furthermore, when analyses of genotype and allele frequencies were stratified by gender, similar nonsignificant results were found. Our study demonstrates a null association between the CD4 C868T polymorphism and an individual's susceptibility of HIV-1 acquisition in a Chinese population. Further studies are warranted to confirm these results.


Assuntos
Antígenos CD4/genética , Linfócitos T CD4-Positivos/imunologia , Suscetibilidade a Doenças , Predisposição Genética para Doença , Infecções por HIV/epidemiologia , Polimorfismo de Nucleotídeo Único , Adulto , China , Feminino , Frequência do Gene , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Análise de Sequência de DNA
20.
PLoS One ; 10(1): e0116479, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25587715

RESUMO

BACKGROUND: Available evidence has demonstrated that osteocalcin may play a role in pathogenesis of cancer, and mutation of the osteocalcin gene may be involved in the cancer development. The aim of this study is to determine whether osteocalcin gene polymorphisms are associated with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) among Chinese population. METHODS: A total of 515 subjects were divided into four groups: 129 patients with chronic hepatitis B (CHB), 62 patients with HBV-related liver cirrhosis (LC), 154 patients with HBV-related HCC, and 170 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect osteocalcin gene rs1800247 and rs1543297 polymorphisms. RESULTS: Compared with healthy controls, the rs1800247 HH and Hh genotypes were associated with a significantly increased susceptibility to HCC (HH versus hh: OR = 6.828, 95% CI 2.620-17.795, P < 0.001; Hh versus hh: OR = 6.306, 95% CI 3.480-11.423, P < 0.001, respectively). Similarly, the subjects bearing the H allele of rs1800247 had more than a 2.4-fold increased risk for development of HCC (OR = 2.484, 95% CI 1.747-3.532, P < 0.001) compared with those bearing the h allele. In addition, we found significant decreased serum osteocalcin levels in HBV-related HCC patients (11.73 ± 8.18 ng/mL) compared with healthy controls (15.3 ± 6.06 ng/mL). Furthermore, the serum osteocalcin levels were significantly lower in HCC patients than healthy controls among the individuals with heterozygous Hh genotype (P = 0.003) and CT genotype (P < 0.001). In contrast, there were no significant differences in the genotype and allele of rs1543297 polymorphisms between the groups of patients and healthy controls. CONCLUSIONS: These findings for the first time suggest that genetic variant in osteocalcin gene rs1800247 polymorphisms may be a risk factor for HBV-related HCC. We also find an inverse association of serum osteocalcin levels with HCC.


Assuntos
Carcinoma Hepatocelular/genética , Hepatite B Crônica/complicações , Neoplasias Hepáticas/genética , Osteocalcina/sangue , Osteocalcina/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/virologia , China , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Vírus da Hepatite B , Hepatite B Crônica/sangue , Hepatite B Crônica/genética , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/genética , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas
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