【摘要】 目的研究人群中胰岛素降解酶基因(IDE)5’-端侧翼的微卫星重复序列多态性与阿尔茨海默病(AD)的相关性。方法采用病例-对照方法研究IDE基因5’-端侧翼的微卫星重复序列多态性、载脂蛋白E(ApoE)基因多态性与AD相关性。选择IDE基因5’端侧翼4个微卫星重复序列位点(CA)n、(AC)nC(GT)n、(CA)n(CT)n、(CA)n,按其基因图谱上的顺序分别给予A、B、D10S583、C为其编号;微卫星片段重复序列多态性的分型是用荧光标记引物PCR法,APOE的基因分型是PCR-RFLP法。结果本研究人群中IDE基因5’端侧翼的4个位点的微卫星片段重复序都有多态性;LOAD病例组和正常对照组中等位基因的分布频率有显著性差别;A208bp与EOAD显著性相关(P=0.0138);APOEε4携带者的频率在LOAD组和对照组分别为52.5%、16.1%(χ2=36.2,P<0.0001,RR=5.76,95%CI=3.17~10.47);APOEε4携带者的频率与EOAD呈显著性相关(P=0.0135);二项逻辑回归分析胰岛素降解酶基因的微卫星重复序列多态性与ApoE基因无显著性意义的相互作用。结论IDE基因5’-端侧翼的微卫星重复序列多态性与晚发型AD的呈显著性相关,支持在染色体10q23-25区域有LOAD候选相关基因的论点,对此区域进行深入研究很有价值。更多还原

【Abstract】 Objective To find the association between the microsatellite repeat polymorphisms of the flank of IDE gene and AD. Methods Case-control method was used to examine microsatellite repeat polymorphisms of IDE gene and the polymorphism of apolipoprotein E (APOE) gene in an ethnically homogeneous Japanese population of 82 LOAD patients, 54 EOAD patients and control of 168 healthy subjects. Four markers of microsatellite repeat were selected on the flank of IDE gene, they were (CA)n, (AC)nC(GT)n, (CA)n(CT)n and (CA)n respectively; according to their order on gene map they were given 4 symbols (A, B, D10S583, C,). Multiplex fluorescent-based genotyping PCR (polymerase chain reaction) was performed to identify microsatellite repeat polymorphisms of IDE gene, and PCR- RFLP(restriction fragment length polymorphism)was performed to determine the genotypes of APOE (Apolipoprotein E) gene. Results Microsatellite polymorphisms were found in these four markers in the study population, and there were significant differences in the allele frequencies of these markers between LOAD cases and controls. These alleles were A 208bp (P<0.0001), B 112bp (P= 0.0012), C 190bp (P=0.032), D10S583 199bp (P=0.0007) and 201bp (P=0.016); and only A 208 bp allele was significantly (P=0.0138) associated with EOAD. The frequency of APOEε4 allele carriers in LOAD cases and control was 52.5 % and 16.1 % (χ2 =36.2, P <0.0001, RR=5.76, 95% CI= 3.17~ 10.47). The frequency of APOEε4 allele carriers was significantly associated with EOAD (P= 0.0135). In binary logistic regression model, no significant interaction was found between IDE gene and APOE gene in LOAD or EOAD.Conclusions These data indicated that there was a significant association of microsatellite repeat polymorphisms of the flank of IDE gene and late-onset Alzheimer’s disease, The presumption is supported, in which there is a candidate gene for LOAD on chromosome 10q 23-25. The ongoing investigation of the genetic source of association and linkage in this region is clearly warranted.更多还原