The candidate polymorphism rs12979860 of interleukin 28B（IL28B） gene was genotyped by means of polymerase chain reaction（PCR） amplification and direct PCR sequencing, and then the role of this single nucleotide po...The candidate polymorphism rs12979860 of interleukin 28B（IL28B） gene was genotyped by means of polymerase chain reaction（PCR） amplification and direct PCR sequencing, and then the role of this single nucleotide polymorphism（SNP） in the response to the treatment of 172 Chinese patients with hepatitis C virus（HCV） chronic infection was analyzed. The results show that the frequencies of major homozygotes（CC） and heterozygotes（CT） of rs12979860 were 0.84 and 0.16, respectively, and the minor homozygotes（TT） wasn’t found in this cohort. A highly significant association was found between the CC genotype and sustained virological response（SVR） in HCV geno type 1 infected patients（P〈0.001） but not in HCV non-genotype 1 infected patients. In addition, a strong association was found between rs12979860 CC genotype and rapid virological response（RVR） in both HCV genotype 1 infected patients（P〈0.001） and non-genotype 1 infected patients（P〈0.001）. Taken together, these results indicate that IL28B polymorphism plays a key role in response to hepatitis C therapy in Chinese patients. Combine assessment of clinical predictors and the IL28B polymorphism may be beneficial to the individualized treatment decision in Asian chronic hepatitis C（CHC） patients.展开更多
LIN28B is an RNA-binding protein that targets a broad range of microRNAs and modulates their maturation and activity.Under normal conditions,LIN28B is exclusively expressed in embryogenic stem cells,blocking different...LIN28B is an RNA-binding protein that targets a broad range of microRNAs and modulates their maturation and activity.Under normal conditions,LIN28B is exclusively expressed in embryogenic stem cells,blocking differentiation and promoting proliferation.In addition,it can play a role in epithelial-to-mesenchymal transition by repressing the biogenesis of let-7 microRNAs.In malignancies,LIN28B is frequently overexpressed,which is associated with increased tumor aggressiveness and metastatic properties.In this review,we discuss the molecular mechanisms of LIN28B in promoting tumor progression and metastasis in solid tumor entities and its potential use as a clinical therapeutic target and biomarker.展开更多
AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 p...AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 patients were included.All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk.End of treatment response(ETR) was defined as loss of detectable serum HCV RNA at the end of treatment.Sustained viral response(SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up.Genotyping of IL28B rs12979860 was performed using the TaqMan assay.We used logistic regression to estimate the adjusted odds ratio(aOR) and 95%CI.RESULTS:The study included 201 HCV-genotype 4 patients.The majority of patients were men(89.6%),with a median age of 47 years,inter-quartile range(40-51).Approximately 62.5% of patients had ETR,and 49.6% had SVR.Individuals who achieved SVR were more likely to be younger(χ 2 = 4.91,P = 0.027),and less likely to have fibrosis(χ 2 = 15.54,P < 0.0001),or inflammation(χ 2 = 7.58,P = 0.006).The genotype distribution of rs12979860 was 36.2%,49.0% and 14.8% for genotypes CC,CT,and TT,respectively.In these participants,rs12979860 genotype distribution did not differ by gender(P = 0.466),pretreatment viral load(P = 0.600),inflammation(P = 0.435),or fibrosis(P = 0.291).The frequencies of IL28B rs12979860 genotypes were TT(14.8%),CT(49.0%),and CC(36.2%).Compared to rs12979860 genotype TT,aORs(95%CI) for ETR and SVR were:CC genotype,[17.55(5.34-57.69) and 5.92(2.09-16.76),respectively];CT genotype,[5.15(1.80-14.78) and 2.48(0.94-6.52),respectively].In the current study,the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC(17.4% and 23.3%,respectively) than individuals who had ETR or SVR(47.9% and 47.2%,respectively).Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype(aOR = 5.92;95%CI:2.09-16.76).Similarly,patients with CT genotype had SVR more often than patients with TT genotype(aOR = 2.48;95%CI:0.94-6.52).Carrying at least one copy of the C allele(genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT(aOR = 7.87;95%CI:2.84-21.82),and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT(aOR = 3.46;95%CI:1.37-8.74).In addition,data were consistent with a significant gene-dose relationship(aOR = 4.05/allele;95%CI:2.27-7.22).The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.CONCLUSION:In HCV-genotype 4 patients,rs12979860 is a sensitive predictor of viral clearance,independent of viral load,age,gender or fibrosis,with no similar relation to severity of fibrosis.展开更多
In a recent genome-wide association study, single nucleotide polymorphisms (SNPs) located near the interleukin-28B gene (IL28B), which encodes type Ⅲ interferon (IFN) λ3, were shown to be strongly associated with a ...In a recent genome-wide association study, single nucleotide polymorphisms (SNPs) located near the interleukin-28B gene (IL28B), which encodes type Ⅲ interferon (IFN) λ3, were shown to be strongly associated with a viral response to pegylated IFNα (PEG-IFNα) and ribavirin (RBV) combination therapy and spontaneous viral clearance in patients chroni-cally and acutely infected with hepatitis C virus (HCV), respectively. The global distribution of allele frequencies shows a remarkable pattern, in which a favorable allele is nearly fixed in East Asia, has an intermediate frequency in Europe, and is least frequent in Africa. Although the under-lying mechanisms responsible for viral responses associated with IL28B SNPs have not been completely elucidated, IFN-stimulated gene expression in patients with unfavorable IL28B genotypes tends to be high at baseline and is insufficiently induced by exogenous IFN administration, resulting in poor treatment outcomes. Clinically, triple therapy with PEG-IFNα/RBV together with direct-acting anti-viral agents (DAAs) is currently used to treat chronic hepatitis C as a first-line therapy. Although the predictive power of IL28B status may be attenuated, the IL28B genotype will remain relevant to the outcomes of DAA therapy when used in combination with PEG-IFNα as a backbone. Even with the introduction of IFN-free therapies with a new class of highly effective DAAs, IL28B SNPs are still useful predictors of treatment outcomes and can be used to individualize treat-ment strategies to maximize cost-effectiveness and identify patients at risk of being refractory to treatment. This review summarizes the current understanding of the clinical sig-nificance and role of IL28B in HCV infection and response to therapy.展开更多
Background:Interleukin-28B (IL-28B) polymorphism is an important predictor for hepatitis C virus (HCV) treatment response.Whether IL-28b genotypes also influence other nontreatment related clinical parameters is uncle...Background:Interleukin-28B (IL-28B) polymorphism is an important predictor for hepatitis C virus (HCV) treatment response.Whether IL-28b genotypes also influence other nontreatment related clinical parameters is unclear.Methods:Patients with HCV-related chronic liver diseases who attended our department during 2012-2014 were retrospectively analyzed.The single nucleotide polymorphisms (SNPs) of rs12979860 (IL-28B) were correlated with various clinical parameters.We also compared these parameters in patients with and without overt diabetes to identify possible associations.Results:A total of 115 patients were included (median age 48,range 15-76 years;70% males).Overall,43/115(37%) patients had chronic hepatitis,while the remaining 72/115 (63%) had cirrhosis.The most common IL-28B genotype was CC,which was found in 53% of patients (61/115),while the remaining 47% were nonCC [CT 42% (48/115) and T-r 5% (6/115)].Clinical and laboratory parameters like Hb,white blood cell (WBC),platelets,bilirubin,transaminases,and albumin were similar in the CC and nonCC genotypes.Overt diabetes mellitus was present in 22% (25/115) of patients.Patients with nonCC genotype had significantly higher prevalence of overt diabetes mellitus than patients with CC genotype (31% [17/54] versus 13% [8/61];p < 0.05).When parameters were compared in patients with and without overt diabetes mellitus,only IL-28B and age were significantly associated with overt diabetes mellitus (p < 0.05).Conclusion:In HCV patients,overt diabetes mellitus was more commonly associated with the nonCC genotype of IL-28B than the CC genotype.Carriers of the T-allele of SNP rs12979860 were more likely to have insulin resistance than CC homozygotes,and this finding may explain the higher prevalence of diabetes in non-CC genotypes.Thus,an IL-28B test may be useful in patients of HCV in order to determine their likelihood of developing diabetes mellitus.展开更多
基金Supported by the State Key Disciplines of Clinical Projects and the National Natural Science Foundation of China (No.30970415)
文摘The candidate polymorphism rs12979860 of interleukin 28B（IL28B） gene was genotyped by means of polymerase chain reaction（PCR） amplification and direct PCR sequencing, and then the role of this single nucleotide polymorphism（SNP） in the response to the treatment of 172 Chinese patients with hepatitis C virus（HCV） chronic infection was analyzed. The results show that the frequencies of major homozygotes（CC） and heterozygotes（CT） of rs12979860 were 0.84 and 0.16, respectively, and the minor homozygotes（TT） wasn’t found in this cohort. A highly significant association was found between the CC genotype and sustained virological response（SVR） in HCV geno type 1 infected patients（P〈0.001） but not in HCV non-genotype 1 infected patients. In addition, a strong association was found between rs12979860 CC genotype and rapid virological response（RVR） in both HCV genotype 1 infected patients（P〈0.001） and non-genotype 1 infected patients（P〈0.001）. Taken together, these results indicate that IL28B polymorphism plays a key role in response to hepatitis C therapy in Chinese patients. Combine assessment of clinical predictors and the IL28B polymorphism may be beneficial to the individualized treatment decision in Asian chronic hepatitis C（CHC） patients.
基金This work was supported by the Fritz Thyssen Foundation(10.21.1.026MN)to L.Meder.
文摘LIN28B is an RNA-binding protein that targets a broad range of microRNAs and modulates their maturation and activity.Under normal conditions,LIN28B is exclusively expressed in embryogenic stem cells,blocking differentiation and promoting proliferation.In addition,it can play a role in epithelial-to-mesenchymal transition by repressing the biogenesis of let-7 microRNAs.In malignancies,LIN28B is frequently overexpressed,which is associated with increased tumor aggressiveness and metastatic properties.In this review,we discuss the molecular mechanisms of LIN28B in promoting tumor progression and metastasis in solid tumor entities and its potential use as a clinical therapeutic target and biomarker.
基金Supported by Hamad Hospital-HMC and Qatar UniversityHealth Sciences-Biomedical Labssponsored by HMC
文摘AIM:To investigate the association between interleukin-28B(IL28B) genotype and response to treatment and hepatic fibrosis in patients with hepatitis C virus(HCV) genotype 4.METHODS:Two hundred and one HCV-genotype 4 patients were included.All patients were treated with Peginterferon alph2a/Ribavirin for 48 wk.End of treatment response(ETR) was defined as loss of detectable serum HCV RNA at the end of treatment.Sustained viral response(SVR) was defined as loss of detectable serum HCV RNA at the end of 24 wk follow up.Genotyping of IL28B rs12979860 was performed using the TaqMan assay.We used logistic regression to estimate the adjusted odds ratio(aOR) and 95%CI.RESULTS:The study included 201 HCV-genotype 4 patients.The majority of patients were men(89.6%),with a median age of 47 years,inter-quartile range(40-51).Approximately 62.5% of patients had ETR,and 49.6% had SVR.Individuals who achieved SVR were more likely to be younger(χ 2 = 4.91,P = 0.027),and less likely to have fibrosis(χ 2 = 15.54,P < 0.0001),or inflammation(χ 2 = 7.58,P = 0.006).The genotype distribution of rs12979860 was 36.2%,49.0% and 14.8% for genotypes CC,CT,and TT,respectively.In these participants,rs12979860 genotype distribution did not differ by gender(P = 0.466),pretreatment viral load(P = 0.600),inflammation(P = 0.435),or fibrosis(P = 0.291).The frequencies of IL28B rs12979860 genotypes were TT(14.8%),CT(49.0%),and CC(36.2%).Compared to rs12979860 genotype TT,aORs(95%CI) for ETR and SVR were:CC genotype,[17.55(5.34-57.69) and 5.92(2.09-16.76),respectively];CT genotype,[5.15(1.80-14.78) and 2.48(0.94-6.52),respectively].In the current study,the patients who did not achieve ETR or SVR had a lower prevalence of rs12979860 CC(17.4% and 23.3%,respectively) than individuals who had ETR or SVR(47.9% and 47.2%,respectively).Individuals with rs12979860 CC genotype had approximately 6 times the odds of SVR compared to individuals with TT genotype(aOR = 5.92;95%CI:2.09-16.76).Similarly,patients with CT genotype had SVR more often than patients with TT genotype(aOR = 2.48;95%CI:0.94-6.52).Carrying at least one copy of the C allele(genotypes CT and CC) had almost 8 times the probability of ETR compared to those with genotype rs12979860 TT(aOR = 7.87;95%CI:2.84-21.82),and approximately 3 times the odds of SVR compared to those with genotype rs12979860 TT(aOR = 3.46;95%CI:1.37-8.74).In addition,data were consistent with a significant gene-dose relationship(aOR = 4.05/allele;95%CI:2.27-7.22).The association between rs12979860 genotype and SVR was similar among those who achieved and those who did not achieve SVR.CONCLUSION:In HCV-genotype 4 patients,rs12979860 is a sensitive predictor of viral clearance,independent of viral load,age,gender or fibrosis,with no similar relation to severity of fibrosis.
文摘In a recent genome-wide association study, single nucleotide polymorphisms (SNPs) located near the interleukin-28B gene (IL28B), which encodes type Ⅲ interferon (IFN) λ3, were shown to be strongly associated with a viral response to pegylated IFNα (PEG-IFNα) and ribavirin (RBV) combination therapy and spontaneous viral clearance in patients chroni-cally and acutely infected with hepatitis C virus (HCV), respectively. The global distribution of allele frequencies shows a remarkable pattern, in which a favorable allele is nearly fixed in East Asia, has an intermediate frequency in Europe, and is least frequent in Africa. Although the under-lying mechanisms responsible for viral responses associated with IL28B SNPs have not been completely elucidated, IFN-stimulated gene expression in patients with unfavorable IL28B genotypes tends to be high at baseline and is insufficiently induced by exogenous IFN administration, resulting in poor treatment outcomes. Clinically, triple therapy with PEG-IFNα/RBV together with direct-acting anti-viral agents (DAAs) is currently used to treat chronic hepatitis C as a first-line therapy. Although the predictive power of IL28B status may be attenuated, the IL28B genotype will remain relevant to the outcomes of DAA therapy when used in combination with PEG-IFNα as a backbone. Even with the introduction of IFN-free therapies with a new class of highly effective DAAs, IL28B SNPs are still useful predictors of treatment outcomes and can be used to individualize treat-ment strategies to maximize cost-effectiveness and identify patients at risk of being refractory to treatment. This review summarizes the current understanding of the clinical sig-nificance and role of IL28B in HCV infection and response to therapy.
文摘Background:Interleukin-28B (IL-28B) polymorphism is an important predictor for hepatitis C virus (HCV) treatment response.Whether IL-28b genotypes also influence other nontreatment related clinical parameters is unclear.Methods:Patients with HCV-related chronic liver diseases who attended our department during 2012-2014 were retrospectively analyzed.The single nucleotide polymorphisms (SNPs) of rs12979860 (IL-28B) were correlated with various clinical parameters.We also compared these parameters in patients with and without overt diabetes to identify possible associations.Results:A total of 115 patients were included (median age 48,range 15-76 years;70% males).Overall,43/115(37%) patients had chronic hepatitis,while the remaining 72/115 (63%) had cirrhosis.The most common IL-28B genotype was CC,which was found in 53% of patients (61/115),while the remaining 47% were nonCC [CT 42% (48/115) and T-r 5% (6/115)].Clinical and laboratory parameters like Hb,white blood cell (WBC),platelets,bilirubin,transaminases,and albumin were similar in the CC and nonCC genotypes.Overt diabetes mellitus was present in 22% (25/115) of patients.Patients with nonCC genotype had significantly higher prevalence of overt diabetes mellitus than patients with CC genotype (31% [17/54] versus 13% [8/61];p < 0.05).When parameters were compared in patients with and without overt diabetes mellitus,only IL-28B and age were significantly associated with overt diabetes mellitus (p < 0.05).Conclusion:In HCV patients,overt diabetes mellitus was more commonly associated with the nonCC genotype of IL-28B than the CC genotype.Carriers of the T-allele of SNP rs12979860 were more likely to have insulin resistance than CC homozygotes,and this finding may explain the higher prevalence of diabetes in non-CC genotypes.Thus,an IL-28B test may be useful in patients of HCV in order to determine their likelihood of developing diabetes mellitus.
