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
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
Pro-apoptotic Bcl-2 protein BAX is an important member of mitochondrial dependent apoptosis regulation and ultimately plays a pivotal role in malignancies. A promoter G(-248)A polymorphism in the TP53 binding region o...Pro-apoptotic Bcl-2 protein BAX is an important member of mitochondrial dependent apoptosis regulation and ultimately plays a pivotal role in malignancies. A promoter G(-248)A polymorphism in the TP53 binding region of BAX results in differential binding capacity of TP53 protein there by regulating its expression, which has been found to be associated with different clinical outcomes in various malignancies. Presently we aimed to analyze the possible impact of the BAX G(-248)A polymorphism on the risk and other clinical features of non-small cell lung cancer in Indian population. The BAX promoter polymorphism was analyzed in blood samples of 320 subjects with 1:1 case/control ratio by primer-introduced restriction analysis PCR and survival curves were plotted using Kaplan-Meier analysis. It was observed that more than 3-fold increased risk of developing non-small cell lung cancer was associated with homozygous AA genotype of BAX G(-248)A promoter polymorphism in Indian population, with more predominant in smokers with pack-year > 45 (heavy) and using cigarette or huka as their smoking source than homozygous GG genotype. Significant associations was observed between TNM stage (p = 0.037) and histological type (0.02), of non-small cell lung cancer patients with the polymorphism. Patients homozygous for A allele exhibited a significant poor overall survival compared with patients displaying GA + AA or GA or GG genotype [median survival 6.0 vs 9.0, 11.0, and 30.0 months, respectively (p < 0.0001)]. Adenocarcinoma and advanced stage patients with AA genotype showed lower median survival time than squamous cell carcinoma and early stage non-small cell lung cancer patients (median 3.0 and 5.0 vs 8.0 and 9.0 months, respectively). We conclude that the genetic polymorphism G(-248)A in the TP53 binding promoter region of pro-apoptotic genes BAX may contribute to the risk of developing non-small cell lung cancer in Indian population and also may be an important factor for adverse clinical outcome for patients with non-small cell lung cancer.展开更多
Background: Self-immunization in systemic lupus is driven by defective in apoptosis. Fas, is an apoptosis-promoting cell surface receptor. The present study evaluate the possible association between APO-1/FAS Promoter...Background: Self-immunization in systemic lupus is driven by defective in apoptosis. Fas, is an apoptosis-promoting cell surface receptor. The present study evaluate the possible association between APO-1/FAS Promoter (-670A/G) Polymorphism and sFAS level with susceptibility to lupus nephritis in SLE patients. Design and Methods: This study was performed on 88 female patients with SLE (mean age, 39.82 ± 10.16 years). 82 patients with lupus nephritis (mean age, 42.50 ± 6.65 years). 150 age and sex-matched person served as controls. All participants were genotyped for the APO-1/FAS Promoter (-670A/G) Polymorphism, manifestations and serum sFAS were correlated with the genotypes. Results: Serum sFAS was significantly higher in patients with -670 AA genotype compared to others. (-670A/G) AA genotype frequencies were significantly higher in the lupus nephritis and SLE patients groups compared with the controls and were associated with increased risk for lupus nephritis and SLE development (odds ratio, 4.08 and 1.91 respectively). Conclusions: The APO-1/FAS Promoter (-670A/G) A allele can be used as a genetic marker for lupus nephritis susceptibility in SLE and was associated with high sFAS level.展开更多
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.
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.
文摘Pro-apoptotic Bcl-2 protein BAX is an important member of mitochondrial dependent apoptosis regulation and ultimately plays a pivotal role in malignancies. A promoter G(-248)A polymorphism in the TP53 binding region of BAX results in differential binding capacity of TP53 protein there by regulating its expression, which has been found to be associated with different clinical outcomes in various malignancies. Presently we aimed to analyze the possible impact of the BAX G(-248)A polymorphism on the risk and other clinical features of non-small cell lung cancer in Indian population. The BAX promoter polymorphism was analyzed in blood samples of 320 subjects with 1:1 case/control ratio by primer-introduced restriction analysis PCR and survival curves were plotted using Kaplan-Meier analysis. It was observed that more than 3-fold increased risk of developing non-small cell lung cancer was associated with homozygous AA genotype of BAX G(-248)A promoter polymorphism in Indian population, with more predominant in smokers with pack-year > 45 (heavy) and using cigarette or huka as their smoking source than homozygous GG genotype. Significant associations was observed between TNM stage (p = 0.037) and histological type (0.02), of non-small cell lung cancer patients with the polymorphism. Patients homozygous for A allele exhibited a significant poor overall survival compared with patients displaying GA + AA or GA or GG genotype [median survival 6.0 vs 9.0, 11.0, and 30.0 months, respectively (p < 0.0001)]. Adenocarcinoma and advanced stage patients with AA genotype showed lower median survival time than squamous cell carcinoma and early stage non-small cell lung cancer patients (median 3.0 and 5.0 vs 8.0 and 9.0 months, respectively). We conclude that the genetic polymorphism G(-248)A in the TP53 binding promoter region of pro-apoptotic genes BAX may contribute to the risk of developing non-small cell lung cancer in Indian population and also may be an important factor for adverse clinical outcome for patients with non-small cell lung cancer.
文摘Background: Self-immunization in systemic lupus is driven by defective in apoptosis. Fas, is an apoptosis-promoting cell surface receptor. The present study evaluate the possible association between APO-1/FAS Promoter (-670A/G) Polymorphism and sFAS level with susceptibility to lupus nephritis in SLE patients. Design and Methods: This study was performed on 88 female patients with SLE (mean age, 39.82 ± 10.16 years). 82 patients with lupus nephritis (mean age, 42.50 ± 6.65 years). 150 age and sex-matched person served as controls. All participants were genotyped for the APO-1/FAS Promoter (-670A/G) Polymorphism, manifestations and serum sFAS were correlated with the genotypes. Results: Serum sFAS was significantly higher in patients with -670 AA genotype compared to others. (-670A/G) AA genotype frequencies were significantly higher in the lupus nephritis and SLE patients groups compared with the controls and were associated with increased risk for lupus nephritis and SLE development (odds ratio, 4.08 and 1.91 respectively). Conclusions: The APO-1/FAS Promoter (-670A/G) A allele can be used as a genetic marker for lupus nephritis susceptibility in SLE and was associated with high sFAS level.
