目的探究中国人群ABCG5/ABCG8基因rs4299376多态性与冠心病的相关性,并对一些相关脂质和脂蛋白水平进行研究,探究其与冠心病的关系。方法收集290例冠心病、198例非冠心病及331例健康正常人的血样,采用核酸自动提取仪提取基因组DNA,MassA...目的探究中国人群ABCG5/ABCG8基因rs4299376多态性与冠心病的相关性,并对一些相关脂质和脂蛋白水平进行研究,探究其与冠心病的关系。方法收集290例冠心病、198例非冠心病及331例健康正常人的血样,采用核酸自动提取仪提取基因组DNA,MassARRAY时间飞行质谱技术分析rs4299376基因型,并测定所有研究对象血脂水平,对比分析各组人群基因多态性及血脂水平差异。结果中国人群ABCG5/ABCG8基因rs4299376多态性在冠心病组与非冠心病组以及健康对照组之间的分布差异无统计学意义。在总体和男性患者中,脂质水平与冠心病没有相关性;但在女性患者中,冠心病患者三酰甘油(TG)及总胆固醇(TC)水平比非冠心病患者高,差异有统计学意义(TG:2.23±1.05 vs 1.84±1.03,P=0.01;TC:4.79±1.17 vs 4.36±1.03,P=0.01)。根据年龄进行分层分析,≥60岁人群中,冠心病患者高密度脂蛋白(HDL)水平比非冠心病患者低(1.09±0.23 vs 1.16±0.25,P=0.03)。结论中国人群ABCG5/ABCG8基因rs4299376多态性与冠心病可能关系不大;女性冠心病患者较非冠心病患者具有更高的TC和TG水平,60岁及以上的冠心病患者较非冠心病患者具有更低的HDL水平。展开更多
目的探讨ABCG5和ABCG8基因在胆囊胆固醇结石和胆固醇息肉发生、发展中的作用。方法回顾性研究2012年3月至2014年3月在中山大学附属第一医院行胆囊切除术的60例患者临床资料。其中男31例,女29例;平均年龄(49±6)岁。所有患者均签署...目的探讨ABCG5和ABCG8基因在胆囊胆固醇结石和胆固醇息肉发生、发展中的作用。方法回顾性研究2012年3月至2014年3月在中山大学附属第一医院行胆囊切除术的60例患者临床资料。其中男31例,女29例;平均年龄(49±6)岁。所有患者均签署知情同意书,符合医学伦理学规定。根据病理学诊断结果,将患者分为胆囊胆固醇结石组(结石组)、胆囊胆固醇息肉组(息肉组)及正常胆囊切除对照组(对照组)。采用实时荧光定量PCR检测胆囊上皮细胞ABCG5和ABCG8 m RNA相对表达量。3组患者m RNA相对表达量的比较采用单因素方差分析和LSD-t检验。结果结石组ABCG5和ABCG8 m RNA相对表达量分别为3.3±0.9和6.9±1.5,明显高于对照组的2.4±0.6和4.3±1.5(LSD-t=23.58,16.55;P<0.05)。息肉组ABCG5和ABCG8 m RNA相对表达量分别为2.6±0.7和4.6±1.3,与对照组比较差异无统计学意义(LSD-t=1.18,0.73;P>0.05)。结论 ABCG5和ABCG8基因可能通过不同机制在胆囊胆固醇结石和胆固醇息肉的发生、发展中发挥作用。展开更多
BACKGROUND Phytosterolemia,also known as sitosterolemia,is a rare autosomal recessive disease characterized by elevated plasma plant sterol levels and xanthomata,which is easily misdiagnosed as familial hypercholester...BACKGROUND Phytosterolemia,also known as sitosterolemia,is a rare autosomal recessive disease characterized by elevated plasma plant sterol levels and xanthomata,which is easily misdiagnosed as familial hypercholesterolemia.Patients with homozygous phytosterolemia often have severe clinical manifestations,with xanthomata in childhood and premature atherosclerosis.Our patient had a milder clinical phenotype.CASE SUMMARY This report describes a patient with homozygous phytosterolemia who presented with only elevated cholesterol and low-density lipoprotein cholesterol(LDL-C)without xanthomata,arteriosclerosis,or hematological abnormalities.Homozygous mutation of ABCG5 which encodes an ATP-binding cassette transporter,was detected by whole exome sequencing and diagnosed as phytosterolemia.Measurement of the patient’s plasma plant sterol levels detected significant elevations in stigmasterol,rapeseed oil-derived plant sterol,andβ-glutaminol levels.Ezetimibe was started and a low plant sterol diet was recommended.The patient’s blood lipid profile was reexamined one month later and showed significant decreases in total cholesterol and LDL-C levels.Phytosterolemia has similar clinical features as familial hypercholesterolemia,is highly susceptible to misdiagnosis,and has a very low incidence,and therefore clinicians need to consider a genetic diagnosis of a definitively hyperlipidemic disorder when statin drugs fail to lower lipid levels.CONCLUSION Phytosterolemia is easily misdiagnosed as familial hypercholesterolaemia and can be treated by dietary modification and cholesterol absorption inhibitors to lower blood lipids.展开更多
文摘目的通过动物实验和体外细胞实验探讨SAK-HV蛋白降胆固醇的机制。方法以0.5mg/kg浓度的SAK-HV蛋白治疗高脂喂养的Apo E-/-C57小鼠,酶法检测Apo E-/-C57小鼠血脂水平,定量PCR法(real-time quantitative PCR,q PCR)和蛋白质印迹(Western blot)法检测小肠ABCG5和ABCG8 m RNA和蛋白的表达水平。100μg/ml的SAK-HV蛋白作用caco-2细胞不同时间后,NBD胆固醇作为荧光探针检测SAK-HV蛋白对caco-2细胞胆固醇吸收的影响,q-PCR和Western blot法检测SAK-HV蛋白对caco-2细胞ABCG5和ABCG8 m RNA和蛋白表达水平的影响。结果 SAK-HV蛋白可以降低高脂喂养的Apo E-/-C57小鼠的血清胆固醇水平,同时上调小肠ABCG5和ABCG8 m RNA和蛋白的表达水平。体外实验表明,SAK-HV蛋白可以抑制caco-2细胞胆固醇的吸收,同时上调ABCG5和ABCG8 m RNA和蛋白的表达水平。结论 SAK-HV蛋白通过上调ABCG5和ABCG8的表达抑制小肠胆固醇的吸收从而降低血清胆固醇水平。
文摘目的探究中国人群ABCG5/ABCG8基因rs4299376多态性与冠心病的相关性,并对一些相关脂质和脂蛋白水平进行研究,探究其与冠心病的关系。方法收集290例冠心病、198例非冠心病及331例健康正常人的血样,采用核酸自动提取仪提取基因组DNA,MassARRAY时间飞行质谱技术分析rs4299376基因型,并测定所有研究对象血脂水平,对比分析各组人群基因多态性及血脂水平差异。结果中国人群ABCG5/ABCG8基因rs4299376多态性在冠心病组与非冠心病组以及健康对照组之间的分布差异无统计学意义。在总体和男性患者中,脂质水平与冠心病没有相关性;但在女性患者中,冠心病患者三酰甘油(TG)及总胆固醇(TC)水平比非冠心病患者高,差异有统计学意义(TG:2.23±1.05 vs 1.84±1.03,P=0.01;TC:4.79±1.17 vs 4.36±1.03,P=0.01)。根据年龄进行分层分析,≥60岁人群中,冠心病患者高密度脂蛋白(HDL)水平比非冠心病患者低(1.09±0.23 vs 1.16±0.25,P=0.03)。结论中国人群ABCG5/ABCG8基因rs4299376多态性与冠心病可能关系不大;女性冠心病患者较非冠心病患者具有更高的TC和TG水平,60岁及以上的冠心病患者较非冠心病患者具有更低的HDL水平。
文摘目的探讨ABCG5和ABCG8基因在胆囊胆固醇结石和胆固醇息肉发生、发展中的作用。方法回顾性研究2012年3月至2014年3月在中山大学附属第一医院行胆囊切除术的60例患者临床资料。其中男31例,女29例;平均年龄(49±6)岁。所有患者均签署知情同意书,符合医学伦理学规定。根据病理学诊断结果,将患者分为胆囊胆固醇结石组(结石组)、胆囊胆固醇息肉组(息肉组)及正常胆囊切除对照组(对照组)。采用实时荧光定量PCR检测胆囊上皮细胞ABCG5和ABCG8 m RNA相对表达量。3组患者m RNA相对表达量的比较采用单因素方差分析和LSD-t检验。结果结石组ABCG5和ABCG8 m RNA相对表达量分别为3.3±0.9和6.9±1.5,明显高于对照组的2.4±0.6和4.3±1.5(LSD-t=23.58,16.55;P<0.05)。息肉组ABCG5和ABCG8 m RNA相对表达量分别为2.6±0.7和4.6±1.3,与对照组比较差异无统计学意义(LSD-t=1.18,0.73;P>0.05)。结论 ABCG5和ABCG8基因可能通过不同机制在胆囊胆固醇结石和胆固醇息肉的发生、发展中发挥作用。
基金Supported by Natural Science Foundation of Heibei Province,No.H2020209160。
文摘BACKGROUND Phytosterolemia,also known as sitosterolemia,is a rare autosomal recessive disease characterized by elevated plasma plant sterol levels and xanthomata,which is easily misdiagnosed as familial hypercholesterolemia.Patients with homozygous phytosterolemia often have severe clinical manifestations,with xanthomata in childhood and premature atherosclerosis.Our patient had a milder clinical phenotype.CASE SUMMARY This report describes a patient with homozygous phytosterolemia who presented with only elevated cholesterol and low-density lipoprotein cholesterol(LDL-C)without xanthomata,arteriosclerosis,or hematological abnormalities.Homozygous mutation of ABCG5 which encodes an ATP-binding cassette transporter,was detected by whole exome sequencing and diagnosed as phytosterolemia.Measurement of the patient’s plasma plant sterol levels detected significant elevations in stigmasterol,rapeseed oil-derived plant sterol,andβ-glutaminol levels.Ezetimibe was started and a low plant sterol diet was recommended.The patient’s blood lipid profile was reexamined one month later and showed significant decreases in total cholesterol and LDL-C levels.Phytosterolemia has similar clinical features as familial hypercholesterolemia,is highly susceptible to misdiagnosis,and has a very low incidence,and therefore clinicians need to consider a genetic diagnosis of a definitively hyperlipidemic disorder when statin drugs fail to lower lipid levels.CONCLUSION Phytosterolemia is easily misdiagnosed as familial hypercholesterolaemia and can be treated by dietary modification and cholesterol absorption inhibitors to lower blood lipids.
