AIM: To identify the two polymorphisms of microsomal triglyceride transfer protein (MTP) gene in the Chinese population and to explore their correlation with both hepatitis B virus (HBV) self-limited infection and per...AIM: To identify the two polymorphisms of microsomal triglyceride transfer protein (MTP) gene in the Chinese population and to explore their correlation with both hepatitis B virus (HBV) self-limited infection and persistent infection. METHODS: A total of 316 subjects with self-limited HBV infection and 316 patients with persistent HBV infection (195 subjects without familial history), matched with age and sex, from the Chinese Han population were enrolled in this study. Polymorphisms of MTP at the promoter region -493 and at H297Q were determined by the allele specific polymerase chain reaction (PCR). RESULTS: The ratio of males to females was 2.13:1 for each group and the average age in the self-limited and chronic infection groups was 38.36 and 38.28 years, respectively. None of the allelic distributions deviated significantly from that predicted by the Hardy-Weinberg equilibrium. There was a linkagedisequilibrium between H297Q and -493G/T (D’ = 0.77). As the χ2 test was used, the genotype distribution of MTP -493G/T demonstrated a significant difference between the self-limited infection group and the entire chronic group or the chronic patients with no family history (χ2 = 8.543, P = 0.015 and χ2 = 7.199, P = 0.019). The allele distribution at the MTP-493 position also demonstrated a significant difference between the study groups without family history (χ2 = 6.212, P = 0.013). The T allele emerged as a possible protective factor which may influence the outcomes of HBV infection (OR: 0.59; 95% CI: 0.389-0.897). CONCLUSION: The polymorphism of the MTP gene, T allele at -493, may be involved in determining the HBV infection outcomes, of which the mechanism needs to be further investigated.展开更多
微粒体甘油三酯转运蛋白MTP(microsomal triglyceride transfer protein,MTP)首先是从牛的肝细胞微粒体碎片中分离获得的,其作用是加速甘油三脂(triglyceride,TG)、胆固醇(cholesteryl ester,CE)和磷脂酰胆碱(phosphatidylcholine,PC)...微粒体甘油三酯转运蛋白MTP(microsomal triglyceride transfer protein,MTP)首先是从牛的肝细胞微粒体碎片中分离获得的,其作用是加速甘油三脂(triglyceride,TG)、胆固醇(cholesteryl ester,CE)和磷脂酰胆碱(phosphatidylcholine,PC)的转运和细胞或亚细胞膜的生物合成。它后来在肝细胞和小肠的微粒体膜中发现[1],由于它的位置及其转运TG可以推测与血浆脂蛋白中极低密度脂蛋白(very low density lipoprotein,VLDL)和乳糜微粒(chylomicrons,CM)的组装过程有关。展开更多
目的:探讨中国汉族人群微粒体甘油三酯转运蛋白(microsomal triglyceride transfer protein,MTP)-493G/T基因多态性与冠心病患病风险的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,测定335例非糖尿病冠心病患者和...目的:探讨中国汉族人群微粒体甘油三酯转运蛋白(microsomal triglyceride transfer protein,MTP)-493G/T基因多态性与冠心病患病风险的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,测定335例非糖尿病冠心病患者和206例无冠心病对照者MTP-493G/T基因多态性。比较两组MTP-493G/T的基因型与等位基因频率的差别,同时观察MTP-493G/T对血脂参数的影响。结果:在中国江苏汉族人群中发现三种基因型,GG型发生频率最高,GT型次之,TT型发生频率最低。冠心病组TT基因型频率(6%)高于对照组(3%)(P<0.05),且T等位基因频率(19%)亦明显高于对照组(12%)(P<0.01)。各基因型与冠状动脉病变支数无明显相关性。TT基因型TG、LDL-C水平高于GG型(P<0.05),而TC、HDL-C和LP(a)水平在两者间无统计学差异(P>0.05)。多因素Logistic回归分析显示TT基因型的OR值为2.14(95%CI1.22～6.56,P=0.014),是独立的危险因素,不依赖TT基因型升高TG、LDL-C的作用。结论:微粒体甘油三酯转运蛋白-493TT基因型可能与冠心病易感性有关,其作用不依赖于TT基因型对TG、LDL-C的影响。展开更多
To explore the relationship between microsomal triglyceride transfer protein (MT P) gene variation and diabetic dyslipidemia among Chinese Methods Using PCR restriction fragment length polymorphism (PCR RFLP) anal...To explore the relationship between microsomal triglyceride transfer protein (MT P) gene variation and diabetic dyslipidemia among Chinese Methods Using PCR restriction fragment length polymorphism (PCR RFLP) analysis and gene sequencing, we studied the influence of a common MTP gene polymorphism in the p romoter region on the apoB containing lipoproteins in 44 Chinese type 2 diabeti c subjects and 32 non diabetic volunteers Results A common functional G/T polymorphism in 493 bp upstream from the transcriptional start point was detected among native Chinese There were 41 carriers (53 9%) of the MTP 493 G/G genotype, 28 (36 8%) of the MTP 493 G/T genotype and 7 (9 3%) of the MTP 493 T/T genotype The allele frequency of M TP 493 T in the diabetic group was 0 30 The MTP 493 T/T diabetic group had significantly higher TG ( P <0 05), VLDL CH ( P <0 05) and smaller LDL pa rticle size ( P <0 001) than the MTP 493 common genotype group Conclusion Genetic variation in the MTP promoter is likely to be highly involved in the pro duction of dyslipidemia in type 2 diabetic subjects展开更多
微粒体甘油三酯转移蛋白(microsomal triglyceride transfer protein,MTP)是一种主要分布于肝细胞、肠上皮细胞中的脂质转移蛋白,其在甘油三酯转运及极低密度脂蛋白组装和分泌中发挥着重要作用。近来研究表明MTP与血脂障碍和肝脏脂肪变...微粒体甘油三酯转移蛋白(microsomal triglyceride transfer protein,MTP)是一种主要分布于肝细胞、肠上皮细胞中的脂质转移蛋白,其在甘油三酯转运及极低密度脂蛋白组装和分泌中发挥着重要作用。近来研究表明MTP与血脂障碍和肝脏脂肪变性等疾病的发生发展关系密切。展开更多
Atherosclerosis is the major complication of diabetes and has become a major issue in the provision of medical care.In particular the economic burden is growing at an alarming rate in parallel with the increasing worl...Atherosclerosis is the major complication of diabetes and has become a major issue in the provision of medical care.In particular the economic burden is growing at an alarming rate in parallel with the increasing worldwide prevalence of diabetes.The major disturbance of lipid metabolism in diabetes relates to the effect of insulin on fat metabolism.Raised triglycerides being the hallmark of uncontrolled diabetes,i.e.,in the presence of hyperglycaemia.The explosion of type 2 diabetes has generated increasing interest on the aetiology ofatherosclerosis in diabetic patients.The importance of the atherogenic properties of triglyceride rich lipoproteins has only recently been recognised by the majority of diabetologists and cardiologists even though experimental evidence has been strong for many years.In the post-prandial phase 50% of triglyceride rich lipoproteins come from chylomicrons produced in the intestine.Recent evidence has secured the chylomicron as a major player in the atherogenic process.In diabetes chylomicron production is increased through disturbance in cholesterol absorption,in particular Neimann Pick C1-like1 activity is increased as is intestinal synthesis of cholesterol through 3-hydroxy-3-methyl glutaryl co enzyme A reductase.ATP binding cassette proteins G5 and G8 which regulate cholesterol in the intestine is reduced leading to chylomicronaemia.The chylomicron particle itself is atherogenic but the increase in the triglyceride-rich lipoproteins lead to an atherogenic low density lipoprotein and low high density lipoprotein.The various steps in the absorption process and the disturbance in chylomicron synthesis are discussed.展开更多
AIM:To investigate the mechanism and in vivo effects of MK-0626,a dipeptidyl peptidase-4 inhibitor,on hepatic steatosis using ob/ob mice.METHODS:We analyzed obese(ob/ob)8-wk-old male mice that had been randomly divide...AIM:To investigate the mechanism and in vivo effects of MK-0626,a dipeptidyl peptidase-4 inhibitor,on hepatic steatosis using ob/ob mice.METHODS:We analyzed obese(ob/ob)8-wk-old male mice that had been randomly divided into two groups of ob/ob mice(n=16 each)and were treated with1.5 or 3 mg/kg MK-0626 and two control groups of untreated ob/ob mice and lean littermates(n=16 each).All mice were fed a normal chow diet with or without MK-0626 for either four or eight weeks.Blood samples were collected,and total hepatectomy was performed.RESULTS:The administration of dietary MK-0626 ameliorated the hepatic lipid accumulation in ob/ob micetreated with 3 mg/kg MK-0626(3 MK),P<0.05,vs untreated ob/ob mice(ob/ob).The MK-0626 treatment reduced the serum alanine aminotransferase levels(both treatment groups,P<0.05 vs ob/ob)and glucoses/insulin levels/calculated HOMA scores(1.5 MK,P<0.05vs ob/ob;3 MK,P<0.01 vs ob/ob)and increased the serum adiponectin levels(3 MK,P<0.05 vs ob/ob)in a dose-dependent manner.The MK-0626 treatment increased the m RNA expression of peroxisome proliferator-activated receptorα/microsomal triglyceride transfer protein(1.5 MK,P<0.05 vs ob/ob;3 MK,P<0.01vs ob/ob)but reduced the sterol regulatory element binding transcription factor-1c/fatty acid synthase/stearoyl-Co A desaturase-1(both treatment groups,P<0.01 vs ob/ob).The MK-0626 treatment increased the activity of AMP-activated protein kinase(AMPK)(both treatment groups,P<0.01 vs ob/ob).CONCLUSION:MK-0626 could attenuate hepatic steatosis through enhancing AMPK activity,inhibiting hepatic lipogenic gene expression,enhancing triglyceride secretion from liver and increasing serum adiponectin levels.展开更多
This study was performed for investigation the relationship between variants of MTP gene polymorphism and the development of NAFLD in patients with and without MS.The study was included 174 NAFLD patients(106 with MS ...This study was performed for investigation the relationship between variants of MTP gene polymorphism and the development of NAFLD in patients with and without MS.The study was included 174 NAFLD patients(106 with MS and 68 without MS),and 141 healthy control subjects.The 493 G/T polymorphism of MTP gene was evaluated by PCR-RFLP method.The frequency of MTP TT genotype and T allele were significantly higher in NAFLD patients when compared to healthy controls.Moreover,a significant association in MTP gene polymorphism was observed in NAFLD patients with MS compared to NAFLD patients without MS and controls.Our study suggested that MTP 493 G/T gene polymorphism may act as susceptibility biomarker for NAFLD and MS.展开更多
基金F.Hoffmann-La Roche Ltd Switzerland and the National High Technology ResearchDevelopment Program of China (863 Program), No. 2006AA02A411
文摘AIM: To identify the two polymorphisms of microsomal triglyceride transfer protein (MTP) gene in the Chinese population and to explore their correlation with both hepatitis B virus (HBV) self-limited infection and persistent infection. METHODS: A total of 316 subjects with self-limited HBV infection and 316 patients with persistent HBV infection (195 subjects without familial history), matched with age and sex, from the Chinese Han population were enrolled in this study. Polymorphisms of MTP at the promoter region -493 and at H297Q were determined by the allele specific polymerase chain reaction (PCR). RESULTS: The ratio of males to females was 2.13:1 for each group and the average age in the self-limited and chronic infection groups was 38.36 and 38.28 years, respectively. None of the allelic distributions deviated significantly from that predicted by the Hardy-Weinberg equilibrium. There was a linkagedisequilibrium between H297Q and -493G/T (D’ = 0.77). As the χ2 test was used, the genotype distribution of MTP -493G/T demonstrated a significant difference between the self-limited infection group and the entire chronic group or the chronic patients with no family history (χ2 = 8.543, P = 0.015 and χ2 = 7.199, P = 0.019). The allele distribution at the MTP-493 position also demonstrated a significant difference between the study groups without family history (χ2 = 6.212, P = 0.013). The T allele emerged as a possible protective factor which may influence the outcomes of HBV infection (OR: 0.59; 95% CI: 0.389-0.897). CONCLUSION: The polymorphism of the MTP gene, T allele at -493, may be involved in determining the HBV infection outcomes, of which the mechanism needs to be further investigated.
文摘微粒体甘油三酯转运蛋白MTP(microsomal triglyceride transfer protein,MTP)首先是从牛的肝细胞微粒体碎片中分离获得的,其作用是加速甘油三脂(triglyceride,TG)、胆固醇(cholesteryl ester,CE)和磷脂酰胆碱(phosphatidylcholine,PC)的转运和细胞或亚细胞膜的生物合成。它后来在肝细胞和小肠的微粒体膜中发现[1],由于它的位置及其转运TG可以推测与血浆脂蛋白中极低密度脂蛋白(very low density lipoprotein,VLDL)和乳糜微粒(chylomicrons,CM)的组装过程有关。
文摘目的:探讨中国汉族人群微粒体甘油三酯转运蛋白(microsomal triglyceride transfer protein,MTP)-493G/T基因多态性与冠心病患病风险的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法,测定335例非糖尿病冠心病患者和206例无冠心病对照者MTP-493G/T基因多态性。比较两组MTP-493G/T的基因型与等位基因频率的差别,同时观察MTP-493G/T对血脂参数的影响。结果:在中国江苏汉族人群中发现三种基因型,GG型发生频率最高,GT型次之,TT型发生频率最低。冠心病组TT基因型频率(6%)高于对照组(3%)(P<0.05),且T等位基因频率(19%)亦明显高于对照组(12%)(P<0.01)。各基因型与冠状动脉病变支数无明显相关性。TT基因型TG、LDL-C水平高于GG型(P<0.05),而TC、HDL-C和LP(a)水平在两者间无统计学差异(P>0.05)。多因素Logistic回归分析显示TT基因型的OR值为2.14(95%CI1.22～6.56,P=0.014),是独立的危险因素,不依赖TT基因型升高TG、LDL-C的作用。结论:微粒体甘油三酯转运蛋白-493TT基因型可能与冠心病易感性有关,其作用不依赖于TT基因型对TG、LDL-C的影响。
文摘To explore the relationship between microsomal triglyceride transfer protein (MT P) gene variation and diabetic dyslipidemia among Chinese Methods Using PCR restriction fragment length polymorphism (PCR RFLP) analysis and gene sequencing, we studied the influence of a common MTP gene polymorphism in the p romoter region on the apoB containing lipoproteins in 44 Chinese type 2 diabeti c subjects and 32 non diabetic volunteers Results A common functional G/T polymorphism in 493 bp upstream from the transcriptional start point was detected among native Chinese There were 41 carriers (53 9%) of the MTP 493 G/G genotype, 28 (36 8%) of the MTP 493 G/T genotype and 7 (9 3%) of the MTP 493 T/T genotype The allele frequency of M TP 493 T in the diabetic group was 0 30 The MTP 493 T/T diabetic group had significantly higher TG ( P <0 05), VLDL CH ( P <0 05) and smaller LDL pa rticle size ( P <0 001) than the MTP 493 common genotype group Conclusion Genetic variation in the MTP promoter is likely to be highly involved in the pro duction of dyslipidemia in type 2 diabetic subjects
文摘Atherosclerosis is the major complication of diabetes and has become a major issue in the provision of medical care.In particular the economic burden is growing at an alarming rate in parallel with the increasing worldwide prevalence of diabetes.The major disturbance of lipid metabolism in diabetes relates to the effect of insulin on fat metabolism.Raised triglycerides being the hallmark of uncontrolled diabetes,i.e.,in the presence of hyperglycaemia.The explosion of type 2 diabetes has generated increasing interest on the aetiology ofatherosclerosis in diabetic patients.The importance of the atherogenic properties of triglyceride rich lipoproteins has only recently been recognised by the majority of diabetologists and cardiologists even though experimental evidence has been strong for many years.In the post-prandial phase 50% of triglyceride rich lipoproteins come from chylomicrons produced in the intestine.Recent evidence has secured the chylomicron as a major player in the atherogenic process.In diabetes chylomicron production is increased through disturbance in cholesterol absorption,in particular Neimann Pick C1-like1 activity is increased as is intestinal synthesis of cholesterol through 3-hydroxy-3-methyl glutaryl co enzyme A reductase.ATP binding cassette proteins G5 and G8 which regulate cholesterol in the intestine is reduced leading to chylomicronaemia.The chylomicron particle itself is atherogenic but the increase in the triglyceride-rich lipoproteins lead to an atherogenic low density lipoprotein and low high density lipoprotein.The various steps in the absorption process and the disturbance in chylomicron synthesis are discussed.
文摘AIM:To investigate the mechanism and in vivo effects of MK-0626,a dipeptidyl peptidase-4 inhibitor,on hepatic steatosis using ob/ob mice.METHODS:We analyzed obese(ob/ob)8-wk-old male mice that had been randomly divided into two groups of ob/ob mice(n=16 each)and were treated with1.5 or 3 mg/kg MK-0626 and two control groups of untreated ob/ob mice and lean littermates(n=16 each).All mice were fed a normal chow diet with or without MK-0626 for either four or eight weeks.Blood samples were collected,and total hepatectomy was performed.RESULTS:The administration of dietary MK-0626 ameliorated the hepatic lipid accumulation in ob/ob micetreated with 3 mg/kg MK-0626(3 MK),P<0.05,vs untreated ob/ob mice(ob/ob).The MK-0626 treatment reduced the serum alanine aminotransferase levels(both treatment groups,P<0.05 vs ob/ob)and glucoses/insulin levels/calculated HOMA scores(1.5 MK,P<0.05vs ob/ob;3 MK,P<0.01 vs ob/ob)and increased the serum adiponectin levels(3 MK,P<0.05 vs ob/ob)in a dose-dependent manner.The MK-0626 treatment increased the m RNA expression of peroxisome proliferator-activated receptorα/microsomal triglyceride transfer protein(1.5 MK,P<0.05 vs ob/ob;3 MK,P<0.01vs ob/ob)but reduced the sterol regulatory element binding transcription factor-1c/fatty acid synthase/stearoyl-Co A desaturase-1(both treatment groups,P<0.01 vs ob/ob).The MK-0626 treatment increased the activity of AMP-activated protein kinase(AMPK)(both treatment groups,P<0.01 vs ob/ob).CONCLUSION:MK-0626 could attenuate hepatic steatosis through enhancing AMPK activity,inhibiting hepatic lipogenic gene expression,enhancing triglyceride secretion from liver and increasing serum adiponectin levels.
基金This work was supported by grant from National Research Centre,Egypt(Project Number 10010205).
文摘This study was performed for investigation the relationship between variants of MTP gene polymorphism and the development of NAFLD in patients with and without MS.The study was included 174 NAFLD patients(106 with MS and 68 without MS),and 141 healthy control subjects.The 493 G/T polymorphism of MTP gene was evaluated by PCR-RFLP method.The frequency of MTP TT genotype and T allele were significantly higher in NAFLD patients when compared to healthy controls.Moreover,a significant association in MTP gene polymorphism was observed in NAFLD patients with MS compared to NAFLD patients without MS and controls.Our study suggested that MTP 493 G/T gene polymorphism may act as susceptibility biomarker for NAFLD and MS.
