载脂蛋白D基因多态与散发性阿尔茨海默病的相关性

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

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，采用病例封照相关性研究方法，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 m5952T／C和rs1568566C／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 χ^2=9．282（P=0．002）；m1568566 χ^2=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m5952和第3号内含子rs15685662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。

Objective To investigate whether polymorphisms of apolipoprotein 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, χ^2 = 9. 282, P = 0. 002 ; rs1568566 adjusted OR = 1. 563, 95% CI 1. 060--2. 306, χ^2 = 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.