北京地区晚发性阿尔兹海默病患者apo E基因多态性与血脂的相关性

Correlation between biochemical parameters and apolipoprotein E genotypes among inpatients with lateonset Alzheimer’s disease in Beijing

目的探讨晚发型阿尔兹海默病(LOAD)患者载脂蛋白E(apo E)基因多态性与血脂水平之间的关系。方法采用基因芯片法检测150例LOAD患者(LOAD组)及150名体检健康者(正常对照组)apo E基因多态性,同时检测总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、小而密低密度脂蛋白胆固醇(sd-LDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白B(apo B)、脂蛋白(a)[Lp(a)]水平。采用多因素非条件Logistic回归分析筛选LOAD的相关危险因素。结果LOAD组E2/3和E3/3基因型频率均低于正常对照组(P<0.05),E3/4和E2/4基因型频率均高于正常对照组(P<0.01)。LOAD组ε3等位基因频率低于正常对照组(P<0.05),ε4等位基因频率高于正常对照组(P<0.01)。与正常对照组比较,LOAD组TC、LDL-C和sd-LDL-C水平明显升高(P<0.01),HDL-C水平明显降低(P<0.01),其他血脂项目差异均无统计学意义(P>0.05)。TC及LDL-C水平在LOAD组ε2、ε3和ε4表型患者中依次升高(P<0.05)。正常对照组ε4表型LDL-C水平明显高于ε2表型(P<0.05)。apo Eε4等位基因和LDL-C升高是LOAD发生的危险因素[比值比(OR)值分别为14.454、5.824,95%可信区间(CI)分别为5.793~16.368、2.582~7.973],HDL-C升高则是LOAD的保护因素(OR=0.020,95%CI为0.006~0.352)。结论apo E基因多态性与脂质代谢密切相关,ε4等位基因可能是LOAD发病的重要遗传因素之一。

Objective To investigate the correlation between the gene polymorphism of apolipoprotein E(apo E)and blood lipid levels in late-onset Alzheimer's disease(LOAD)patients.Methods The apo E gene polymorphism was determined by gene chip in 150 LOAD patients and 150 healthy subjects.Total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),small and dense low-density lipoprotein cholesterol(sd-LDL-C),high-density lipoprotein cholesterol(HDL-C),apolipoprotein B(apo B)and lipoprotein(a)[Lp(a)]levels were also determined.Multivariate unconditional Logistic regression analysis was used to screen the related risk factors of LOAD.Results The frequencies of E2/3 and E3/3 genotypes in LOAD group were lower than those in healthy control group(P<0.05),and the frequencies of E3/4 and E2/4 genotypes were higher than those in healthy control group(P<0.01).The frequency ofε3 allele in LOAD group was lower than that in healthy control group(P<0.05),and the frequency ofε4 allele in LOAD group was higher than that in healthy control group(P<0.01).Compared with healthy control group,the levels of TC,LDL-C and sd-LDL-C were increased(P<0.01),while HDL-C was decreased(P<0.01)in LOAD group.There was no statistical significance in the other blood lipids(P>0.05).The levels of TC and LDL-C were gradually increased in LOAD patients with the phenotypes ofε2,ε3 andε4(P<0.05).The LDL-C level ofε4 phenotype was higher than that ofε2 phenotype in healthy control group(P<0.05).The apo Eε4 allele and LDL-C were the risk factors for LOAD,the odds ratios(OR)were 14.454 and 5.824,and 95%confidence intervals(CI)were 5.793-16.368 and 2.582-7.973,respectively.HDL-C was the protective factor for LOAD(OR=0.020,95%CI 0.006-0.352).Conclusions The apo E gene polymorphism is closely related to lipid metabolism,and the apo Eε4 allele may be one of the important genetic factors in the pathogenesis of LOAD.