载脂蛋白D基因多态与散发性阿尔茨海默病的相关性

目的 通过检测载脂蛋白D基因(apolipoprotein D gene,ApoD)单核苷酸多态位点,探讨其与北方汉族人群散发性阿尔茨海默病(sporadic Alzheimer's disease,SAD)的相关性.方法 应用聚合酶链反应(PCR)及直接测序筛查ApoD基因所有外显子及其两端内含子多态位点.选取等位基因频率大于10%的位点,利用PCR-限制性片段长度多态性(PCR-RFLP)技术,采用病例-对照相关性研究方法 ,研究256例SAD患者以及294名健康人的ApoD多态位点与SAD发病的关系.同时对位点间的连锁不平衡及构建的单体型进行相关性分析.结果 ApoD第2号外显子存在T/C多态性(rs5952),第3号内含子(rs1568566)存在C/T多态性.ApoD rs5952 T/C和rs1568566 C/T等位基因频率和基因型频率在SAD组和对照组间的分布差异有统计学意义.Logistic回归分析表明携带rs5952C或rs1568566T等位基因分别增加SAD发病风险:校正后rs5952 χ2=9.282(P=0.002);rs1568566 χ2=5.072(P=0.024).进一步分析证实性别和ApoD多态性存在交互作用.rs5952-rs1568566位点间存在连锁不平衡.结论 北方汉族人ApoD基因存在第2号外显子rs5952和第3号内含子rs1568566 2个多态位点;ApoD多态可增加SAD发病风险;携带rs5952T或rs1568566C单体型可能对SAD的发病有一定的保护作用.

Association between apolipoprotein D gene polymorphisms and sporadic Alzheimer's disease

Objective To investigate whether polymorphisms of apolipopretein D gene (APOD) have an effect on the risk for sporadic Alzheimer's disease (SAD).Methods Combination of polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing technique to screen all exons (1-5),along with flanking exon-intron boundaries of the ApoD gene.We investigated the polymorphisms of ApoD in 256 SAD patients and 294 healthy controls from North China by PCR-RFLP technique.Association of every polymorphism with AD was analyzed in this case-control study.Results Two ApoD (rs5952 and rs1568566) polymorphisms were detected and there were significant differences in the genotype or allele frequencies for the 2 ApoD polymorphisms respectively between cases and controls.Logistic analysis showed that rs5952C or rs1568566T allele carrier increased the risk for SAD (rs5952 adjusted OR=1.817,95% CI 1.237--2.669,χ2=9.282,P=0.002 ; rs1568566 adjusted OR=1.563,95% CI 1.060-2.306,χ2=5.072,P=0.024).The APOD polymorphisms showed gender specific associations.The linkage disequilibrium of the 2 single nucleotide polymorphism loci was found between rs5952 and rs1568566 of ApoD.Conclusion Polymorphisms of rs5952 and rs1568566 in APOD might play an important role in modifying risk for SAD.