第10号染色体上CA重复序列的多态性与阿尔茨海默病的相关性研究

Correlation Study on the CA Repeats Polymorphism on Chromosome 10 with Alzheimer's Disease

目的 近年的研究报道显示在第10号染色体上有多个位点与阿尔茨海默病(Alzheimer’sdisease,AD)相关,其中10q23—25区域是个研究的热点。我们的目的是想在这个区域找到与AD相关的位点或基因。方法 我们采用病例一对照方法在日本人群中研究D10S583上游16kb的CA重复序列的多态性和载脂蛋白E基因与AD相关性,病例组139人,健康对照组171人。结果 在AD病例组和正常对照组中等位基因206携带者的频率分别是41.9％和19％,其差别有显著性(X^2=18.46,P<0.0001,RR=3.06,95％CI=1.82～5.15);而208携带者的频率在AD组中是46.0％,在对照组中是70.8％,其差别有显著性(X^2=19.41,P<0.0001,RR=0.35,95％CI=0.22～0.56)。结论 CA重复序列等位基因206的频率与AD呈正相关,而208则呈负相关,这个结果支持在10q23—25区域有AD候选基因的论点。根据报道还有其他多个AD假定候选基因被定位在这个区域,因此值得对这个区域进行深入研究。

Objective Several independent studies have reported that loci on chromosome 10 are associated with Alzheimer's disease (AD) , the region of q1023-25 is the hot spot. Our aim is to find new marker in this region, which is associated with AD. Methods By using case-control method we examined CA repeats on the upstream 16kb of the D10S583 marker and apolipoprotein E ( APOE) gene in an ethnically homogeneous Japanese population of 139 AD patients and the control of 171 healthy subjects. Results The frequencyies of 206 allele carriers in cases and controls are 41. 9% ,19% respectively, and there is a significant difference(x2 = 18. 46, P < 0. 000 1 ,RR=3. 06,95%CI= 1. 82-5. 15) ; The frequencies of 208 allele carriers in cases and controls are 46. 0% and 70. 8% respectively, and there is also a significant difference(x2 =19. 41, P<0. 000 1, RR=0. 35,95%CI=0. 22-0. 56). Conclusions These data indicated that the frequency of 206 allele is positively associated with AD, and the effect of 208 allele is inverse. The presumption is supported, in which there is a candidate gene for AD in this region of chromosome 10. It is reported that a number of other putative candidate genes are also located in this region. The ongoing investigation of the genetic source of association and linkage in this region is clearly warranted.