胆固醇酯转运蛋白基因D442G多态位点对阿尔茨海默病易感性的影响及机制分析

The effect of cholesteryl ester transfer protein D442G polymorphism on Alzheimer′s disease and serum HDL level

目的探讨胆固醇酯转运蛋白(CETP)基因D442G多态位点对阿尔茨海默病(AD)和血清高密度脂蛋白(HDL)水平的影响。方法用限制性片段长度多态性检测107例AD和115名对照D442G和载脂蛋白E(ApoE)的基因多态性,测定其血清HDL水平。结果对照组D442G的DG基因型频率高于AD组;ApoE分层后ApoEε4携带者D442G的DG基因型在对照组的频率高于AD组,而ApoEε4非携带者2组间无统计学差异,ApoEε4携带者的DG基因型的HDL水平高于DD基因型。结论 D442G是AD保护性因素,其机制可能与其对HDL水平的影响有关。

Objective To investigate the effect of the cholesteryl ester transfer protein D442G polymorphism on sporadic Alzheimer′s disease（SAD） and serum HDL level.Methods The genotypes of CETP（D442G） and apolipoprotein E（ApoE） in 107 AD and 115 age and gender-matched healthy elders were determined by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP） analysis.The serum HDL level was measured.Results The frequency of D442G heterozygote was higher in control subjects than that in AD patients.When the sample was stratified by APOE allele status,the frequency of D442G heterozygote was also higher in control subjects than that in AD patients in the present of APOE ε4,whereas there was no significant difference between control subjects and AD patinets among APOE ε4 noncarriers.Among APOE ε4 carriers,the serum HDL level of DG genotype was higher than that of DD genotype.Conclusions Our results indicate that CETP（D442G） polymorphism may independently decrease the risk of AD,and this protective role is depended on G allele compensating the lower HDL level.