APOE基因多态性与阿尔茨海默病的相关性研究

Association of Apolipoprotein E Polymorphism and Sporadic Alzheimer's Disease

目的分析载脂蛋白E（APOE）基因多态性是否与散发性阿尔茨海默病（AD）存在关联；探讨APOE基因多态性对血脂、脂蛋白代谢的影响及在AD发病中的作用。方法运用多重引物等位特异PCR法检测77例散发性AD患者和158例非痴呆（ND）对照组中APOE基因型和等位基因频率；简易智能精神状态检查量表对AD研究对象进行评分，并测定血浆中的TC，TG，HDL-C，LDL-C，apoE，apoA和apoB的浓度。结果①AD和ND组携带ε4的基因型频率分别为20.8％和9.5％，两组差别有统计学意义（X^2=5.758，P=0.016，OR=2.501，95％CI为1.163－5.376）；APOEε4等位基因频率AD组（11．7％）高于ND对照组（5．1％），差异具有统计学意义（X^2=6.772，P=0.009）。②AD组血浆TC，HDL-C，LDL-C，apoE，apoB水平均明显低于ND组（P均等于0.000）；血浆TG和apoA水平在两组中差异无统计学意义；APOEε2，ε3和ε4组间血浆TC，TG和HDL-C水平差异有统计学意义；与ε3相比，ε4使TC和HDL-C水平降低，TG水平升高，ε2则使TC和TG水平降低，HDL-C水平升高，提示APOE基因型调控血脂的代谢。③校正年龄、性别后，APOEε4等位基因是AD发生的危险因素（OR=3.990，95％CI为1.527-10.425，P=0.005）；HDL-C则是AD的保护因素（OR=0．062，95％CI为0．014-0．270，P=0.000）；携带APOEε4的基因型与HDL-C无交互作用（HDL-C ＊ genotype P=0．596）。结论APOEε4等位基因，HDL-C与散发性AD有关联，APOEε4可能是散发性AD发病的危险因素，并建议把APOEε4和HDL-C等作为散发性AD的生物标记。

Objective To explore whether the polymorphism of apolipoprotein E （APOE） gene are associated with sporadic Alzheimer＇s Disease（AD）,and whether influence of APOE genotypes on lipids and apolipoprotein metabolism and it is a risk of sporadic AD. Methods APOE genotypes were analyzed by using multi allele-specific primer PCR. Mini-Mental State Examination scores for both patients with AD and ND subjects. The concentration of serum TC,TG,HDL-C,LDL- C,apoE,apoA and apoB were measured in fasting blood samples. Results①APOE ε4 genotype frequency was in AD subjects（20.8%） was significantly higher than in ND subjects （9.5%）（X^2=5.785,P=0.016,OR=2. 501,95% CI 1.163-5.376）. Allele frequency of APOE E4 was in AD subjects （11.7%） was significantly higher than in ND subjects （5.1%） （X^2= 6.772,P=0.009）. ②The concentration of serum TC,HDL-C,LDL-C,apoE and apoB in AD subjects were significant lower than in ND subjects （all P=0.000）. The concentration of TG and apoA were not statistical difference between sporadic AD and ND （P〉0.05）. The concentration of serum TC,TG and HDL-C were statistically significant differences in the subjects with APOE ε2 ,ε3 and ε4. APOE ε4 allele had been associated with high TG level and with a decreased level of TC and HDL-C relative to ε3 allele,but the APOE ε2 allele had been associated with high HDL-C level and with a decreased level of TC and TG relative to ε3 allele. Data suggested APOE genotypes probably regulated lipid and apolipoprotein metabolism. ③Controlling age and gender, Logistic regression analysis showed that APOE ε4 allele was a risk factor （OR=3.990,95% CI 1.527-10.425,P=0.005） and HDL-C was a protection factor （OR=0.062,95% CI 0.014-0.270,P=0.000） for sporadic AD. There was no interaction effect between APOE ε4 genotype and HDL-C（HDL-C ＊ genotype P=0. 596）. Conclusion Data suggest that APOE ε4 allele and HDL-C are associated with sporadic AD. APOE ε4 allele might be a risk factor in AD and play a major role in the onset of sporadic AD. The results suggest that APOE ε4 allele and HDL-C can be used as biomarkers of AD.