载脂蛋白E的基因多态性与冠心病的关系及对阿托伐他汀调脂消斑的影响
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摘要
研究背景和目的：近年来研究发现，个体的基因型决定其对环境因素的易感性。遗传基因载脂蛋白E(apolipoprotein E，apoE)在血脂代谢中起重要作用，apoE基因多态性与冠心病易感性之间存在相关性其各基因型与冠心病严重程度和血脂质代谢水平有较密切的关系。我们应用聚合酶链反应——限制性片段长度多态性(Polymerase chain eaction-restricted fragment length polmorphism，PCR-RELP)方法，检测了121例冠心病患者的基因型，目的在于研究基因遗传变异apoE基因多态性对冠心病他汀类药物调脂消斑的影响。①通过对冠心病患者apoE基因型的检测，探讨载脂蛋白E基因多态性与冠心病相关因素的关联性②通过对冠心病患者阿托伐他汀治疗前后血脂水平的检测研究apoE基因多态性对调脂治疗的影响③研究apoE基因多态性对阿托伐他汀治疗冠心病冠状动脉硬化斑块的消除的影响，为冠心病的防治提供了新思路和新方法。
研究对象和方法：①采用PCR-RELP)测定西京医院心内科的住院冠心病患者121例基因型，分析研究apoE基因多态性与冠心病的相关因素的关联性。②他汀类药物(阿托伐他汀10mg 1次／d)调脂治疗95例，血脂治疗6个月治疗前后分析apoE基因多态性对他汀类药物调脂的影响。③33例患者他汀类药物(阿托伐他汀10mg 1次／d治疗疗程6个月，冠状动脉造影检测治疗前后冠状动脉粥样硬化斑块的消退与
第四军医大学硕士学位论文
即。E基因型的相关性。
结果:①aPoE基因型分布:所有研究对象aPoE PCR片段均得
到满意扩增，特异性片段为233bp。共检测到5个基因型:EZ/2(2例)、
E3/2(18例)、E3/3(52例)、E3/4(44例)和E4/4(5)例。未检测到EZ/4
基因型。将5个基因型归并为3组:。2E2/2+EZ/3、￡3E3/3、。4
E314十E4/4等位基因相对频率为17%、43%、40%。②aPoE基因型的
相关因素。E3/4+E4/4型冠心病发病年龄明显偏低(P<0.05)，早发
冠心病组E4等位基因频率分别为(40%)较迟发组(9%)显著增高，
E3则较低(17%vs35%)，2组相差显著(P<0.01)，EZ/2、E3/2例数
较少，未行统计学分析。E3/4十E414型组间吸烟率差异无显著性，而
冠脉狭窄较其他基因型间更为严重，冠脉多发狭窄的比率在E3/4+E4/4
也显著增加。(P<0.05)。E3/4+E4/4组，总胆固醇(TC)和低密度脂
蛋白胆固醇和(LDL一C)显著高于其他基因型组，(P<0.01)，甘油三
脂(TG)与高密度脂蛋白胆固醇(HDL一C)在各基因型组无显著差异。
③aPoE基因型的多态性与阿托伐他汀调脂治疗相关.各基因型组中，
与E3/4+E4/4相比较TC和LDL一C水平降低(P<0.05);HDL一C升高，
各基因型组无显著差异。TG的变化不显，无统计学意义。④阿托伐
他汀治疗6个月后，冠状动脉粥样硬化斑块的消退与aPoE基因型各
组间有显著差异(P<0.05)，各组内治疗前后无显著差异(P>.05)。
结论:①aPoE基因多态性与冠心病早发严重度和血脂水平相关。
②apoE的基因多态性与调脂及冠脉狭窄的治疗相关。③在冠心病患者
和有危险因素的人群中开展apoE的检查，不仅为早期发现、预防和
治疗冠心病提供依据，还可作为监测和评估病情变化的指标。④阿托
伐他汀具有延缓粥样硬化斑块进展的作用。
BACKGROUND AND OBJECTIVE:Recently,studies have show that gene type of individual decided susceptibility on environment factor .Genetic factors play an important role in serum lipid metabolism, apolipoprotein E (apoE) polmorphism have relativity with susceptibility to Coronary heart Disease (CHD) in defferent gene type as well as to CHD severity and level of lipid metabolism Polymerase chain eaction-restricted fragment length polmorphism was used to test 121 patients gene type with CHD .To explore the effect of apolipoprotein E Polmorphism on Coronary heart Disease Therapy That were Lipid-regulated and atherosclerotic Plaques .To investigate the assosiations between apolipoprotein E (apoE) polmorphism and coronary heart disease(CHD) by examine patient ' s apoE genes.To explore the new direction in Cardiology and provide new methods on preventing (1) To investigate the assosiations between apolipoprotein E (apoE) polmorphism and coronary heart disease(CHD) by examine patient' s apoE genes.(2)Respectively to ch
eck serum lipid of patient with CHD that
were givened atorvastation before and half a year later, at the same time,to analyze the effecter of apoE polmorphism on lipid-regulating therpy. (3)To explore the role that apoE polmorphism affected the effect in coronary atherosclerotic plaque retard by atorvastation.
METHODS: (1) Using Polymerase chain reaction -restricted fragment length polmorphism (PCR-RELP),measuring 121 patients'genes with CHD that was in Department of Cardiovasology ,Xijing hospital and analyzing assosiation between apoE polmorphism and CHD. (2) 95patients were given atorvastatin 10mg day-1 and respectively check plasma Lipid levels before and 6 months later,to observe the efficacy of apoE polmorphism on lipid-regulating. (3)Before 33patients were given atorvastatin 10mg day-1 and 6 months Later,they all underwent CAG (Coronary Angiography), survey coronary atherosclerotic plaque retard and pertinence with ApoE polmorphism by QCA (Quantitative Coronary Angiography,)
RESULTS: (1) apoE genotype distributing:all patient' s apoE fragment were amplified by PCR satisfaction.specical fragment were 233bp.5 genotypes were found. They were genotype E2/2(2cases) E3/2 (18 cases) E3/3 (52 cases) E3/4 ( 44 cases) E4/4( 5 cases). But genotype E2/4 was not found. 5 genotypes were mergered 3 groups. They were E2/2+ E3/2 E3/3 and E3/4+E4/4 groups respectively.The alleles frequencies were 17% 43% and40% respectively .Among them,early onset CHD group with E4 Alleles frequencies < 40%) was higer than aged group (9%) .E3 was lower (17%vs35%) Significant difference were observed between 2 groups (P<0.01) .Patient with E2/2 and E3/2 were fewer,so they were not analysed. (2)ApoE genotype correlation factor. Early-onset CHD ratio in genotype E3/4+E4/4 is lower (P<0.05) and there is no significant difference between three groups in smoking franks,but
frequence of multiatherosclerotic plaques were significantly higher (P<0.05) .In E3/4+E4/4 group,TC and LDLch were higher than other genotype (P<0.01) . there was no significant difference on TG and HDLc in each genotyoe. (3) ApoE polmorphism was asscosiation on lipid-regulating of Atorvastatin. To compare E3/4+E4/4 genotype group ,the levels of TC and LDLch were receder and it was significant difference.but no significant difference on HDLc highten and TG depressed. (4) After patients were given Atorvastatin and 6 months later,coronary atherosclerotic plaques therapy was association with genotype.there was significant difference between each groups.But it was no significant difference in each group.
CONCLUTION: (1)ApoE polmorphism was associated with more extensive in early-onset CHD and levels of serum lipid. (2) ApoE polmorphism was also associated lipid-regulating and coronary atherosclerotic plaque therpy. (3)During patients with CHD and persons with CHD risk factors,Measuring ApoE genotype ,these methods can provide evidences of CHD in earlier period,also can monitor patient' s condition and prognosis (4)The result demonstrate that atorvastatin had the role of re
研究对象和方法：①采用PCR-RELP)测定西京医院心内科的住院冠心病患者121例基因型，分析研究apoE基因多态性与冠心病的相关因素的关联性。②他汀类药物(阿托伐他汀10mg 1次／d)调脂治疗95例，血脂治疗6个月治疗前后分析apoE基因多态性对他汀类药物调脂的影响。③33例患者他汀类药物(阿托伐他汀10mg 1次／d治疗疗程6个月，冠状动脉造影检测治疗前后冠状动脉粥样硬化斑块的消退与
第四军医大学硕士学位论文
即。E基因型的相关性。
结果:①aPoE基因型分布:所有研究对象aPoE PCR片段均得
到满意扩增，特异性片段为233bp。共检测到5个基因型:EZ/2(2例)、
E3/2(18例)、E3/3(52例)、E3/4(44例)和E4/4(5)例。未检测到EZ/4
基因型。将5个基因型归并为3组:。2E2/2+EZ/3、￡3E3/3、。4
E314十E4/4等位基因相对频率为17%、43%、40%。②aPoE基因型的
相关因素。E3/4+E4/4型冠心病发病年龄明显偏低(P<0.05)，早发
冠心病组E4等位基因频率分别为(40%)较迟发组(9%)显著增高，
E3则较低(17%vs35%)，2组相差显著(P<0.01)，EZ/2、E3/2例数
较少，未行统计学分析。E3/4十E414型组间吸烟率差异无显著性，而
冠脉狭窄较其他基因型间更为严重，冠脉多发狭窄的比率在E3/4+E4/4
也显著增加。(P<0.05)。E3/4+E4/4组，总胆固醇(TC)和低密度脂
蛋白胆固醇和(LDL一C)显著高于其他基因型组，(P<0.01)，甘油三
脂(TG)与高密度脂蛋白胆固醇(HDL一C)在各基因型组无显著差异。
③aPoE基因型的多态性与阿托伐他汀调脂治疗相关.各基因型组中，
与E3/4+E4/4相比较TC和LDL一C水平降低(P<0.05);HDL一C升高，
各基因型组无显著差异。TG的变化不显，无统计学意义。④阿托伐
他汀治疗6个月后，冠状动脉粥样硬化斑块的消退与aPoE基因型各
组间有显著差异(P<0.05)，各组内治疗前后无显著差异(P>.05)。
结论:①aPoE基因多态性与冠心病早发严重度和血脂水平相关。
②apoE的基因多态性与调脂及冠脉狭窄的治疗相关。③在冠心病患者
和有危险因素的人群中开展apoE的检查，不仅为早期发现、预防和
治疗冠心病提供依据，还可作为监测和评估病情变化的指标。④阿托
伐他汀具有延缓粥样硬化斑块进展的作用。
BACKGROUND AND OBJECTIVE:Recently,studies have show that gene type of individual decided susceptibility on environment factor .Genetic factors play an important role in serum lipid metabolism, apolipoprotein E (apoE) polmorphism have relativity with susceptibility to Coronary heart Disease (CHD) in defferent gene type as well as to CHD severity and level of lipid metabolism Polymerase chain eaction-restricted fragment length polmorphism was used to test 121 patients gene type with CHD .To explore the effect of apolipoprotein E Polmorphism on Coronary heart Disease Therapy That were Lipid-regulated and atherosclerotic Plaques .To investigate the assosiations between apolipoprotein E (apoE) polmorphism and coronary heart disease(CHD) by examine patient ' s apoE genes.To explore the new direction in Cardiology and provide new methods on preventing (1) To investigate the assosiations between apolipoprotein E (apoE) polmorphism and coronary heart disease(CHD) by examine patient' s apoE genes.(2)Respectively to ch
eck serum lipid of patient with CHD that
were givened atorvastation before and half a year later, at the same time,to analyze the effecter of apoE polmorphism on lipid-regulating therpy. (3)To explore the role that apoE polmorphism affected the effect in coronary atherosclerotic plaque retard by atorvastation.
METHODS: (1) Using Polymerase chain reaction -restricted fragment length polmorphism (PCR-RELP),measuring 121 patients'genes with CHD that was in Department of Cardiovasology ,Xijing hospital and analyzing assosiation between apoE polmorphism and CHD. (2) 95patients were given atorvastatin 10mg day-1 and respectively check plasma Lipid levels before and 6 months later,to observe the efficacy of apoE polmorphism on lipid-regulating. (3)Before 33patients were given atorvastatin 10mg day-1 and 6 months Later,they all underwent CAG (Coronary Angiography), survey coronary atherosclerotic plaque retard and pertinence with ApoE polmorphism by QCA (Quantitative Coronary Angiography,)
RESULTS: (1) apoE genotype distributing:all patient' s apoE fragment were amplified by PCR satisfaction.specical fragment were 233bp.5 genotypes were found. They were genotype E2/2(2cases) E3/2 (18 cases) E3/3 (52 cases) E3/4 ( 44 cases) E4/4( 5 cases). But genotype E2/4 was not found. 5 genotypes were mergered 3 groups. They were E2/2+ E3/2 E3/3 and E3/4+E4/4 groups respectively.The alleles frequencies were 17% 43% and40% respectively .Among them,early onset CHD group with E4 Alleles frequencies < 40%) was higer than aged group (9%) .E3 was lower (17%vs35%) Significant difference were observed between 2 groups (P<0.01) .Patient with E2/2 and E3/2 were fewer,so they were not analysed. (2)ApoE genotype correlation factor. Early-onset CHD ratio in genotype E3/4+E4/4 is lower (P<0.05) and there is no significant difference between three groups in smoking franks,but
frequence of multiatherosclerotic plaques were significantly higher (P<0.05) .In E3/4+E4/4 group,TC and LDLch were higher than other genotype (P<0.01) . there was no significant difference on TG and HDLc in each genotyoe. (3) ApoE polmorphism was asscosiation on lipid-regulating of Atorvastatin. To compare E3/4+E4/4 genotype group ,the levels of TC and LDLch were receder and it was significant difference.but no significant difference on HDLc highten and TG depressed. (4) After patients were given Atorvastatin and 6 months later,coronary atherosclerotic plaques therapy was association with genotype.there was significant difference between each groups.But it was no significant difference in each group.
CONCLUTION: (1)ApoE polmorphism was associated with more extensive in early-onset CHD and levels of serum lipid. (2) ApoE polmorphism was also associated lipid-regulating and coronary atherosclerotic plaque therpy. (3)During patients with CHD and persons with CHD risk factors,Measuring ApoE genotype ,these methods can provide evidences of CHD in earlier period,also can monitor patient' s condition and prognosis (4)The result demonstrate that atorvastatin had the role of re
引文
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