家族聚集性与非家族聚集性脑梗死患者载脂蛋白E基因多态性研究(英文)

Genetic polymorphism of apolipoprotein E in patients with family aggregation or non-family aggregation of cerebral infarction

背景:载脂蛋白E(apolipoproteinE,ApoE)基因多态性与脑梗死的关系,多数学者认为ApoEε4等位基因是脑梗死的遗传易患因素之一,而有部分学者却认为与脑梗死无关。目的:探讨ApoE基因多态性与家族聚集性和非家族聚集性脑梗死的关系。设计:病例对照研究。地点和对象:实验地点为江苏南通医学院附属医院神经内科。对象均来源于南通医学院神经内科就诊确诊的脑梗死患者66例,其中家族中无脑卒中史的脑梗死患者40例,家族中有明确脑梗死先证者的家族聚集性脑梗死患者26例。对照组选择江苏地区无血缘关系的健康汉族人群90例。干预:应用PCR扩增ApoE基因第4外显子包含编码第11位和第158位氨基酸残基的基因序列,cfoI限制性内切酶切后电泳,银染色分析ApoE基因型,同时检测3组人群的血脂、脂蛋白(a)及部分载脂蛋白。主要观察指标:基因型频率、等位基因频率、血清各脂质含量。结果:脑梗死组ε3/4基因型频率(30%)较对照组(9%)明显增加,而ε3/3基因型频率(50%)明显低于对照组(76%),差异有显著统计学意义(χ2=35.85,P<0.01);脑梗死组ε4等位基因频率(21%)高于对照组(6%),而ε3等位基因频率(71%)低于对照组(87%),差异有显著统计学意义(χ2=35.85,P<0.01)。两脑梗死组之间。

BACKGROUND:Most researchers believe that apolipoprotein E (ApoE) allele is genetic facilitated factor of cerebral infarction(CI)which is denied by some other researchers. OBJECTIVE:To investigate the relationship between the polymorphism of ApoE gene and family aggregation and non-family aggregation of CI. DESIGN:A case controlled study. SETTING and PARTICIPANTS:This experiment was carried out at the Department of Neurology,Affiliated Hospital of Nantong Medical University in Jiangsu.Sixty-six patients were diagnosed as CI,amongst which 40 cases denied positive familial CI history and 26 patients displayed definite family aggregation of CI.Ninty healthy natives of Jiangsu city of Han nationality without kinship were recruited as controls. INTERVENTIONS:PCR technique was used to amplify the fourth exon of ApoE gene containing codes for the 11th and 158th amino acid residue,and then the amplified products were cleaved with cfoI endonuclease before eletrophoresis and silver staining for analyzing ApoE genotype. At the same time, serum lipid,lipoprotein and partly apolipoprotein of three groups were determined. MAIN OUTCOME MEASURES:Genotype frequency,allele frequency and content of serum lipids. RESULTS:The frequency of ε3/4 was 30%in the CI group,obviously higher than 9%in the control group, but the frequency of ε3/3 was 50%,obviously lower than 76%in the control group ,the differences were statistically significant(χ2=35.85,P< 0.01);The allele frequency of ε4 was 21%in the CI group,higher than 6%in the control group,but the allele frequency of ε3 was 71%, significantly lower than 87%in the control group(χ2=35.85,P< 0.01).The genotype frequency of ε3/4 and the allele frequency of ε4 presented ascending tendency in family aggregation of CI group NFACI group in contrast with non-family aggregation of CI group(NFACI group),while the frequency of ε3/4 and ε4 decreased,difference between the two groups was insignificant.The same lipid metabolic abnormality could be observed in both CI groups,total serum cholesteral(TC),low density lipoprotein(LDL),apolipoprotein B(ApoB) and lipoprotein(a) of NFACI group were significantly higher than corresponding subjects of control group(P< 0.01),and high density lipoprotein(HDL) of FACI group obviously lower than that of NFACI group and control group(P< 0.01and P< 0.05),but the difference between the later two groups was of no statistical significance. CONCLUSION:ApoE3/4 genotype is involved in the occurrence of CI andε4 is one of the genetic facilitated factors. ε3 allele plays an protective role in the occurrence of CI;ApoE polymorphism and HDL-C cooperatively involved in the occurrence of CI.