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
Background &Aims: Hepatic steatosis is frequent in chronic hepatitis C. Several mechanisms might be implicated, including metabolic cofactors and direct viral effects on intracellular lipid pathways. In a transgen...Background &Aims: Hepatic steatosis is frequent in chronic hepatitis C. Several mechanisms might be implicated, including metabolic cofactors and direct viral effects on intracellular lipid pathways. In a transgenic mouse model, hepatitis C virus (HCV) was shown to inhibit microsomal triglyceride transfer protein (MTP) activity, which is essential for hepatic lipoprotein assembly and secretion. No data are available on liver MTP activity in HCV-infected patients. We therefore investigated liver MTP gene expression and its lipid transfer activity in untreated cases infected with the major HCV genotypes showing variable degrees of hepatic steatosis. Methods: MTP messenger RNA (mRNA) levels were measured by real-time polymerase chain reaction, and MTP activity was assessed by fluorescent assay in liver biopsy specimens of 58 HCV-positive patients. A set of metabolic and serum lipid markers was also measured at the time of liver biopsies. Results: MTP mRNA levels showed a statistically significant (P = .001) inverse correlation with the degree of steatosis, independently of the HCV genotype. MTP mRNA levels also had an inverse correlation with serum insulin (P = .0002), homeostasis model assessment-insulin resistance (HOMA-IR) (P = .005), and body mass index (P = .02) in patients with HCV-1 and HCV-2 and with serum HCV-RNA (P = .02) in HCV-3 patients. Liver MTP-specific activity was significantly reduced in HCV-3 patients compared with those with other HCV genotypes (P = .004) and correlated with reduced serum cholesterol, apo B, and low-density lipoproteins. Conclusions: MTP may play a central role in HCV-related steatosis, being modulated by different genotype-specific mechanisms, mainly hyperinsulinemia in non-HCV-3 patients, and more profound and direct virus-related effects in HCV-3-infected individuals.展开更多
微粒体甘油三酯转运蛋白（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运蛋白，在甘油三酯转运以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与非酒精性脂肪性肝...微粒体甘油三酯转运蛋白（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运蛋白，在甘油三酯转运以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与非酒精性脂肪性肝病的发生发展关系密切。展开更多
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Background &Aims: Hepatic steatosis is frequent in chronic hepatitis C. Several mechanisms might be implicated, including metabolic cofactors and direct viral effects on intracellular lipid pathways. In a transgenic mouse model, hepatitis C virus (HCV) was shown to inhibit microsomal triglyceride transfer protein (MTP) activity, which is essential for hepatic lipoprotein assembly and secretion. No data are available on liver MTP activity in HCV-infected patients. We therefore investigated liver MTP gene expression and its lipid transfer activity in untreated cases infected with the major HCV genotypes showing variable degrees of hepatic steatosis. Methods: MTP messenger RNA (mRNA) levels were measured by real-time polymerase chain reaction, and MTP activity was assessed by fluorescent assay in liver biopsy specimens of 58 HCV-positive patients. A set of metabolic and serum lipid markers was also measured at the time of liver biopsies. Results: MTP mRNA levels showed a statistically significant (P = .001) inverse correlation with the degree of steatosis, independently of the HCV genotype. MTP mRNA levels also had an inverse correlation with serum insulin (P = .0002), homeostasis model assessment-insulin resistance (HOMA-IR) (P = .005), and body mass index (P = .02) in patients with HCV-1 and HCV-2 and with serum HCV-RNA (P = .02) in HCV-3 patients. Liver MTP-specific activity was significantly reduced in HCV-3 patients compared with those with other HCV genotypes (P = .004) and correlated with reduced serum cholesterol, apo B, and low-density lipoproteins. Conclusions: MTP may play a central role in HCV-related steatosis, being modulated by different genotype-specific mechanisms, mainly hyperinsulinemia in non-HCV-3 patients, and more profound and direct virus-related effects in HCV-3-infected individuals.
