AIM: To study Helicobacter pylori (H pylori) infection in relation to E-cadherin (E-cad) promoter polymorphism and hypermethylation in GCs.METHODS: Specimens were taken from representative cancerous lesions and adjace...AIM: To study Helicobacter pylori (H pylori) infection in relation to E-cadherin (E-cad) promoter polymorphism and hypermethylation in GCs.METHODS: Specimens were taken from representative cancerous lesions and adjacent non-cancerous epithelia of 67 resected GCs. Hpyloriwas detected by real-time PCR of the cagA gene from non-neoplastic epithelium.E-cad promoter polymorphism and hypermethylation were determined by restriction fragment length polymorphism analysis and methylation-specific PCR, respectively. Expression of E-cad protein was determined by immunohistochemistry.RESULTS: Hpyloriwas found in 57% of patients with GC.H pylori infection was more frequently found in tumors with the -160C/C genotype than those with the -160C/A and -160A/A genotypes (74% vs47%, P = 0.02). Hpylori infection was associated with E-cad methylation in nonneoplastic epithelium; however, no significant difference in H pylori was observed between methylated and unmethylated cancerous lesions.CONCLUSION: Patients with the -160C/C genotype might require Hpyloriinfection to promote the inactivation of CDH1, suggesting that Hpylori infection might affect GC in an initial stage because polymorphism is germ line.Mechanism of hypermethylation of CDH1 promoter in GC is complex, and Hpyloriinfection might affect it in an initial stage.展开更多
Previous studies reported the association between interleukin-6(IL-6)-174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus(T2DN).However,the results remain controversial.In the pre...Previous studies reported the association between interleukin-6(IL-6)-174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus(T2DN).However,the results remain controversial.In the present study,we conducted a meta-analysis to further examine this relationship between IL-6-174G/C gene polymorphism and T2DN.Three databases(PubMed,SinoMed and ISI Web of Science)were used to search clinical case-control studies about IL-6-174G/C polymorphism and T2DN published until Apr.14,2018.Fixed-or random-effects n lodels were used to calculate the effect sizes of odds ratio(OR)and 95%confide nee intervals(95%CI).Moreover,subgroup analysis was performed in tenns of the excretion rate of albuminuria.All the statistical analyses were con ducted using Stata 12.0.A total of 11 case-control studies were included in this study,involving 1203 cases of T2DN and 1571 cases of T2DM without DN.Metaanalysis showed that there was an association between IL-6-174G/C polymorphism and increased risk of T2DN under the allelic and recessive genetic models(G vs.C:OR=1.10,95%CI 1.03-1」&P=0.006;GG vs.CC+GC:OR=1.11,95%CI 1.02-1.21,P=0.016).In the subgroup analysis by albuminuria,a significant association of IL-6-174G/C polymorphism with risk of T2DN was noted in the microalbuminuria group under the recessive model(OR=1.54,95%CI 1.02-2.32,P=0.038).In conclusion,this meta-analysis suggests that IL-6-174G/C gene polymorphism is associated with the risk of T2DN.展开更多
AIM: To investigate whether single-nucleotide polymor- phisms in the promoter regions of endotoxin-responsive genes CD14 C (-159) T is associated with chronic hepatitis B. METHODS: We obtained genomic DNA from 80 pati...AIM: To investigate whether single-nucleotide polymor- phisms in the promoter regions of endotoxin-responsive genes CD14 C (-159) T is associated with chronic hepatitis B. METHODS: We obtained genomic DNA from 80 patients with established diagnosis of chronic hepatitis B and 126 healthy subjects served as a control population. The CD 14 C (-159) T polymorphism was investigated using an allele specific PCR method. RESULTS: Twenty seven percent of chronic hepatitis B patients and 75% of controls were heterozygous for CT genotype. The difference between the chronic hepatitis B and control groups was statistically significant [P < 0.0001; Odds ratio (OR) = 2.887; 95% CI: 1.609-5.178]. Twenty four point six percent of chronic hepatitis B and patients 12.3% of the control group were heterozygous for TT genotype. The difference between groups was not statistically significant (P = 0.256; OR = 0.658; 95% CI: 0.319-1.358). Forty eight point four percent of chronic hepatitis B patients and 12.7% of control were homozy- gote for CC genotype (P < 0.004; OR = 0.416; 95% CI: 0.229-0.755). The frequency of allele C was 61.9% and allele T was 38.1% in hepatitis B patients group. The frequency of allele C was 55.2% and allele T was 44.8% for the control group (P = 0.179; OR = 1.319; 95% CI: 0.881-1.977). CONCLUSION: The TT heterozygous genotype was not a risk factor for chronic hepatitis B. CC homozygote genotype is protective for hepatitis B. Lack of heterozy- gosis of genotype CT is a risk factor for chronic hepatitis B. Alleles C or T were not risk factors for chronic hepatitis B. These findings show the role of a single-nucleotide polymorphism at CD14/-159 on the development ofchronic hepatitis B. Endotoxin susceptibility may play a role in the pathogenesis of chronic hepatitis B.展开更多
BACKGROUND Chronic hepatitis C(CHC)is associated with type 2 diabetes mellitus.Although the pathogenesis remains to be elucidated,a growing evidence has suggested a role of pro-inflammatory immune response.Increased s...BACKGROUND Chronic hepatitis C(CHC)is associated with type 2 diabetes mellitus.Although the pathogenesis remains to be elucidated,a growing evidence has suggested a role of pro-inflammatory immune response.Increased serum concentrations of Interleukin 6(IL-6)have been associated with insulin resistance,type 2 diabetes mellitus as well as advanced forms of liver disease in chronic hepatitis C infection.AIM To investigate the frequency of IL-6-174G/C(rs1800795)single nucleotide polymorphism(SNP)in CHC patients and in healthy subjects of the same ethnicity.Associations between type 2 diabetes mellitus(dependent variable)and demographic,clinical,nutritional,virological and,IL-6 genotyping data were also investigated in CHC patients.METHODS Two hundred and forty-five patients with CHC and 179 healthy control subjects(blood donors)were prospectively included.Type 2 diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association.Clinical,biochemical,histological and radiological methods were used for the diagnosis of the liver disease.IL-6 polymorphism was evaluated by Taqman SNP genotyping assay.The data were analysed by logistic regression models.RESULTS Type 2 diabetes mellitus,blood hypertension and liver cirrhosis were observed in 20.8%(51/245),40.0%(98/245)and 38.4%(94/245)of the patients,respectively.The frequency of the studied IL-6 SNP did not differ between the CHC patients and controls(P=0.81)and all alleles were in Hardy-Weinberg equilibrium(P=0.38).In the multivariate analysis,type 2 diabetes mellitus was inversely associated with GC and CC genotypes of IL-6-174(OR=0.42;95%CI=0.22-0.78;P=0.006)and positively associated with blood hypertension(OR=5.56;95%CI=2.79-11.09;P<0.001).CONCLUSION This study was the first to show that GC and CC genotypes of IL-6-174 SNP are associated with a decreased risk of type 2 diabetes mellitus in patients chronically infected with hepatitis C virus.The identification of potential inflammatory mediators involved in the crosstalk between hepatitis C virus and the axis pancreas-liver remains important issues that deserve further investigations.展开更多
基金Supported by Clinical Research Fund of the Tri-Service General Hospital CY Foundation for Advancement of Education, Science and Medicine, Taipei, Taiwan, China
文摘AIM: To study Helicobacter pylori (H pylori) infection in relation to E-cadherin (E-cad) promoter polymorphism and hypermethylation in GCs.METHODS: Specimens were taken from representative cancerous lesions and adjacent non-cancerous epithelia of 67 resected GCs. Hpyloriwas detected by real-time PCR of the cagA gene from non-neoplastic epithelium.E-cad promoter polymorphism and hypermethylation were determined by restriction fragment length polymorphism analysis and methylation-specific PCR, respectively. Expression of E-cad protein was determined by immunohistochemistry.RESULTS: Hpyloriwas found in 57% of patients with GC.H pylori infection was more frequently found in tumors with the -160C/C genotype than those with the -160C/A and -160A/A genotypes (74% vs47%, P = 0.02). Hpylori infection was associated with E-cad methylation in nonneoplastic epithelium; however, no significant difference in H pylori was observed between methylated and unmethylated cancerous lesions.CONCLUSION: Patients with the -160C/C genotype might require Hpyloriinfection to promote the inactivation of CDH1, suggesting that Hpylori infection might affect GC in an initial stage because polymorphism is germ line.Mechanism of hypermethylation of CDH1 promoter in GC is complex, and Hpyloriinfection might affect it in an initial stage.
文摘Previous studies reported the association between interleukin-6(IL-6)-174G/C gene polymorphism and the risk of diabetic nephropathy in type 2 diabetes mellitus(T2DN).However,the results remain controversial.In the present study,we conducted a meta-analysis to further examine this relationship between IL-6-174G/C gene polymorphism and T2DN.Three databases(PubMed,SinoMed and ISI Web of Science)were used to search clinical case-control studies about IL-6-174G/C polymorphism and T2DN published until Apr.14,2018.Fixed-or random-effects n lodels were used to calculate the effect sizes of odds ratio(OR)and 95%confide nee intervals(95%CI).Moreover,subgroup analysis was performed in tenns of the excretion rate of albuminuria.All the statistical analyses were con ducted using Stata 12.0.A total of 11 case-control studies were included in this study,involving 1203 cases of T2DN and 1571 cases of T2DM without DN.Metaanalysis showed that there was an association between IL-6-174G/C polymorphism and increased risk of T2DN under the allelic and recessive genetic models(G vs.C:OR=1.10,95%CI 1.03-1」&P=0.006;GG vs.CC+GC:OR=1.11,95%CI 1.02-1.21,P=0.016).In the subgroup analysis by albuminuria,a significant association of IL-6-174G/C polymorphism with risk of T2DN was noted in the microalbuminuria group under the recessive model(OR=1.54,95%CI 1.02-2.32,P=0.038).In conclusion,this meta-analysis suggests that IL-6-174G/C gene polymorphism is associated with the risk of T2DN.
文摘AIM: To investigate whether single-nucleotide polymor- phisms in the promoter regions of endotoxin-responsive genes CD14 C (-159) T is associated with chronic hepatitis B. METHODS: We obtained genomic DNA from 80 patients with established diagnosis of chronic hepatitis B and 126 healthy subjects served as a control population. The CD 14 C (-159) T polymorphism was investigated using an allele specific PCR method. RESULTS: Twenty seven percent of chronic hepatitis B patients and 75% of controls were heterozygous for CT genotype. The difference between the chronic hepatitis B and control groups was statistically significant [P < 0.0001; Odds ratio (OR) = 2.887; 95% CI: 1.609-5.178]. Twenty four point six percent of chronic hepatitis B and patients 12.3% of the control group were heterozygous for TT genotype. The difference between groups was not statistically significant (P = 0.256; OR = 0.658; 95% CI: 0.319-1.358). Forty eight point four percent of chronic hepatitis B patients and 12.7% of control were homozy- gote for CC genotype (P < 0.004; OR = 0.416; 95% CI: 0.229-0.755). The frequency of allele C was 61.9% and allele T was 38.1% in hepatitis B patients group. The frequency of allele C was 55.2% and allele T was 44.8% for the control group (P = 0.179; OR = 1.319; 95% CI: 0.881-1.977). CONCLUSION: The TT heterozygous genotype was not a risk factor for chronic hepatitis B. CC homozygote genotype is protective for hepatitis B. Lack of heterozy- gosis of genotype CT is a risk factor for chronic hepatitis B. Alleles C or T were not risk factors for chronic hepatitis B. These findings show the role of a single-nucleotide polymorphism at CD14/-159 on the development ofchronic hepatitis B. Endotoxin susceptibility may play a role in the pathogenesis of chronic hepatitis B.
基金Fundationde AmparoàPesquisa do Estado de Minas Gerais,No.APQ-02320-18.
文摘BACKGROUND Chronic hepatitis C(CHC)is associated with type 2 diabetes mellitus.Although the pathogenesis remains to be elucidated,a growing evidence has suggested a role of pro-inflammatory immune response.Increased serum concentrations of Interleukin 6(IL-6)have been associated with insulin resistance,type 2 diabetes mellitus as well as advanced forms of liver disease in chronic hepatitis C infection.AIM To investigate the frequency of IL-6-174G/C(rs1800795)single nucleotide polymorphism(SNP)in CHC patients and in healthy subjects of the same ethnicity.Associations between type 2 diabetes mellitus(dependent variable)and demographic,clinical,nutritional,virological and,IL-6 genotyping data were also investigated in CHC patients.METHODS Two hundred and forty-five patients with CHC and 179 healthy control subjects(blood donors)were prospectively included.Type 2 diabetes mellitus was diagnosed according to the criteria of the American Diabetes Association.Clinical,biochemical,histological and radiological methods were used for the diagnosis of the liver disease.IL-6 polymorphism was evaluated by Taqman SNP genotyping assay.The data were analysed by logistic regression models.RESULTS Type 2 diabetes mellitus,blood hypertension and liver cirrhosis were observed in 20.8%(51/245),40.0%(98/245)and 38.4%(94/245)of the patients,respectively.The frequency of the studied IL-6 SNP did not differ between the CHC patients and controls(P=0.81)and all alleles were in Hardy-Weinberg equilibrium(P=0.38).In the multivariate analysis,type 2 diabetes mellitus was inversely associated with GC and CC genotypes of IL-6-174(OR=0.42;95%CI=0.22-0.78;P=0.006)and positively associated with blood hypertension(OR=5.56;95%CI=2.79-11.09;P<0.001).CONCLUSION This study was the first to show that GC and CC genotypes of IL-6-174 SNP are associated with a decreased risk of type 2 diabetes mellitus in patients chronically infected with hepatitis C virus.The identification of potential inflammatory mediators involved in the crosstalk between hepatitis C virus and the axis pancreas-liver remains important issues that deserve further investigations.
