Objective：To investigate a possible association of LMP2/LMP7 genes with chronic hepatitis C virus（HCV） infection,and to assess whether LMP2/LMP7 genes could influence the outcomes of HCV infection among drug users....Objective：To investigate a possible association of LMP2/LMP7 genes with chronic hepatitis C virus（HCV） infection,and to assess whether LMP2/LMP7 genes could influence the outcomes of HCV infection among drug users.Methods：Genomic DNAs of 362 anti-HCV sero-positive drug users and 225 control drug users were extracted from the peripheral blood leukocytes.The sero-positive patients were divided into those who had persistent infection and those who had spontaneously cleared the infection.Polymorphisms of LMP genes were determined by PCR combined with restriction fragment length polymorphism（RFLP）.Results：The distribution of LMP2 genotypes among the control,persistent infection and spontaneous clearance groups were not different.However,the LMP7 codon 145 Gln/Lys,Lys/Lys,and Gln/Lys＋Lys/Lys genotypes were found significantly more frequent in the persistent infection group than in control group（OR=1.75,95%CI=1.06～2.90;OR=3.16,95%CI=1.23-8.12;OR=1.94,95%CI=1.21-3.12,respectively）.Similarly,the frequencies of the codon 145 Gln/Lys,Lys/Lys,and Gln/Lys＋Lys/Lys genotypes were found significantly more frequent in the persistent infection group than in the spontaneous clearance group（OR=1.64,95%CI=1.04-2.57;OR=2.40,95%CI=1.09-5.28;OR=1.76,95%CI=1.152.69,respectively）.Stratified analysis indicated that combined genotype Gln/Lys＋Lys/Lys of the LMP7 gene was related to an increasing susceptibility to HCV infection（OR=1.91,95%CI=1.02-3.55;OR=2.19,95%CI=1.243.89;OR=1.91,95%CI=1.05-3.48,OR=2.86,95%CI=1.41-5.78,respectively）and the risk of persistent HCV infection（OR=1.94,95%CI=1.12-3.34;OR=2.02,95%CI=1.21-3.38;OR=1.78,95%CI=1.12-2.85,OR=2.23,95%CI=1.09-4.58,respectively）among30-year-old,males,the injection drug user（IDU）subjects and/or the shorter duration drug users（≤5 y）.Conclusion：These results suggest that polymorphism of the LMP7 gene may have an influence on the outcomes of HCV infection,and is one of the factors accounting for the genetic susceptibility to HCV infection among drug users.展开更多
Host genetic factors may predict the outcome and treatment response in hepatitis C virus（HCV）infection.One of these factors is the single nucleotide polymorphisms of the interleukin 28B（IL28B）gene.We sought to eva...Host genetic factors may predict the outcome and treatment response in hepatitis C virus（HCV）infection.One of these factors is the single nucleotide polymorphisms of the interleukin 28B（IL28B）gene.We sought to evaluate the outcome of pegylated interferon and ribavirin therapy in association with IL-28B rs8099917 and rsl2980275 in patients infected with HCV genotype 4.A total of 180 patients with chronic hepatitis C were selected from Egyptians who have received combined therapy with pegylated interferon and ribavirin for 6 months and their response was evaluated after follow-up at 0,6,12,24 and 48 weeks from the beginning of the therapy.Blood samples were collected from responders and non-responders.Genomic DNA was extracted from whole blood and genotyping was carried out by polymerase chain reaction and restriction fragment length polymorphism（PCR-RFLP）.Our results showed that TT genotype of rs8099917 was associated with higher sustained viral response（SVR）rates and G allele represented a risk factor for failure of response（OR=3.7,CI=1.8：7.64）while rs12980275 was not significantly associated with SVR in genotype 4 Egyptian patients.The determination of 1L-28B SNPs may be useful in enhancing correct prediction of SVR achievement in treating this group of genotype 4 patients.展开更多
Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilit...Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms（SNP） in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type（WT） apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin（unrelated to apoA-V function） may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.展开更多
基金supported by the National Mega-project of Science Research Project(No.2008ZX10002-013 and No.2009ZX1004-904)
文摘Objective：To investigate a possible association of LMP2/LMP7 genes with chronic hepatitis C virus（HCV） infection,and to assess whether LMP2/LMP7 genes could influence the outcomes of HCV infection among drug users.Methods：Genomic DNAs of 362 anti-HCV sero-positive drug users and 225 control drug users were extracted from the peripheral blood leukocytes.The sero-positive patients were divided into those who had persistent infection and those who had spontaneously cleared the infection.Polymorphisms of LMP genes were determined by PCR combined with restriction fragment length polymorphism（RFLP）.Results：The distribution of LMP2 genotypes among the control,persistent infection and spontaneous clearance groups were not different.However,the LMP7 codon 145 Gln/Lys,Lys/Lys,and Gln/Lys＋Lys/Lys genotypes were found significantly more frequent in the persistent infection group than in control group（OR=1.75,95%CI=1.06～2.90;OR=3.16,95%CI=1.23-8.12;OR=1.94,95%CI=1.21-3.12,respectively）.Similarly,the frequencies of the codon 145 Gln/Lys,Lys/Lys,and Gln/Lys＋Lys/Lys genotypes were found significantly more frequent in the persistent infection group than in the spontaneous clearance group（OR=1.64,95%CI=1.04-2.57;OR=2.40,95%CI=1.09-5.28;OR=1.76,95%CI=1.152.69,respectively）.Stratified analysis indicated that combined genotype Gln/Lys＋Lys/Lys of the LMP7 gene was related to an increasing susceptibility to HCV infection（OR=1.91,95%CI=1.02-3.55;OR=2.19,95%CI=1.243.89;OR=1.91,95%CI=1.05-3.48,OR=2.86,95%CI=1.41-5.78,respectively）and the risk of persistent HCV infection（OR=1.94,95%CI=1.12-3.34;OR=2.02,95%CI=1.21-3.38;OR=1.78,95%CI=1.12-2.85,OR=2.23,95%CI=1.09-4.58,respectively）among30-year-old,males,the injection drug user（IDU）subjects and/or the shorter duration drug users（≤5 y）.Conclusion：These results suggest that polymorphism of the LMP7 gene may have an influence on the outcomes of HCV infection,and is one of the factors accounting for the genetic susceptibility to HCV infection among drug users.
文摘Host genetic factors may predict the outcome and treatment response in hepatitis C virus（HCV）infection.One of these factors is the single nucleotide polymorphisms of the interleukin 28B（IL28B）gene.We sought to evaluate the outcome of pegylated interferon and ribavirin therapy in association with IL-28B rs8099917 and rsl2980275 in patients infected with HCV genotype 4.A total of 180 patients with chronic hepatitis C were selected from Egyptians who have received combined therapy with pegylated interferon and ribavirin for 6 months and their response was evaluated after follow-up at 0,6,12,24 and 48 weeks from the beginning of the therapy.Blood samples were collected from responders and non-responders.Genomic DNA was extracted from whole blood and genotyping was carried out by polymerase chain reaction and restriction fragment length polymorphism（PCR-RFLP）.Our results showed that TT genotype of rs8099917 was associated with higher sustained viral response（SVR）rates and G allele represented a risk factor for failure of response（OR=3.7,CI=1.8：7.64）while rs12980275 was not significantly associated with SVR in genotype 4 Egyptian patients.The determination of 1L-28B SNPs may be useful in enhancing correct prediction of SVR achievement in treating this group of genotype 4 patients.
基金Supported by a grant from NIH(R37-HL64159)an AHA Postdoctoral Fellowship Award(VS)
文摘Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）homeostasis.Whereas a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms（SNP） in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type（WT） apoA-V may have therapeutic benefit.It is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG clearance.On the other hand,subjects with hypertriglyceridemia of independent origin（unrelated to apoA-V function） may not respond to apoA-V augmentation in this manner.Improvement in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic strategy.Candidates would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.
