摘要
目的 探索中国人群胆固醇24S-羟化酶（CYP46）基因第二内含子T／C多态性与晚发性阿尔茨海默病（晚发性AD）的相关性及其与apoEε4共同对晚发性AD发病风险的影响。方法 应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法，检测99例散发性晚发性AD患者（≥65岁）和113例健康对照者CYP46基因和载脂蛋白（ApoE）基因，观察其多态性分布，然后进行Odd Ratio分析和率值的显著性检测。结果 （1）CYP46基因的3种基因型和2个等位基因频率在case-control两组间比较，差异有统计学意义，其中T多态性与晚发性AD有显著性关联（P〈0．01）；（2）在apoEε4携带者和非携带者中，CYP46基因T等位基因与晚发性AD有显著性关联（P〈0．01）；（3）Odd Ratio分析，携带CYP46基因TT基因型者患晚发性AD的风险值为2．40，携带apoEε4者为1．62，而同时携带两风险基因时，晚发性AD风险值最高为12．94。结论 CYP46基因C／T多态性与中国人晚发性AD发病相关，同时携带有apoEε4和CYP46基因TT基因型，有发生晚发性AD的最高风险，提示apoEε4和CYP46基因在晚发性AD发病机制中可能有协同作用。
Objective To investigate the association between the T/C polymorphism of the second intron of cholesterol 24S- hydroxylase （CYP46） gene and late onset Alzheimer disease （LOAD）. Methods Ninety-nine sporadic LOAD patients （≥65 years old） and 113 healthy control individuals were enrolled, and polymorphism distribution of the CYP46 gene and apolipoprotein E （apoE） gene were detected by using polymerase chain reaction-restrictive fragment length polymorphism （PCR-RFLP）. The detections of odd ratio and its chi-square significance were used. Remits （1）Significant differences in frequencies of the three genotypes and two alleles of CYP46 gene between the case and control groups were found, and T allele was associated with LOAD （P〈0. 01）. （2）All subjects were stratified into apoE ε4 carrier and apoE ε4 non-carrier, and a case-control analysis was held. T allele and TT homozygotes were associated with LOAD （P〈0. 01）. CYT46 gene T allele frequency was significant higher in LOAD group than in healthy control group （P 〈0. 05）. （3）Odd ratio analysis showed that the individuals with only CYP46 gene TT genotype had higher relative risk of LOAD （OR=2.40）, OR=1.62 in the carriers with only apoEε4; Moreover, the risk of LOAD reached the highest （OR=12.94） for the individuals who carried the both risk alleles. Conclusions CYP46 gene C/T polymorphism is associated with LOAD in Chinese population, the individuals who carried apoEε4 and CYP46 gene TT genotype have the highest LOAD risk. It suggests that ApoEε4 and CYP46 gene have synergistic action in the pathogenesis of LOAD.
出处
《中华老年医学杂志》
CAS
CSCD
北大核心
2007年第1期13-15,共3页
Chinese Journal of Geriatrics
基金
国家重点基础研究发展973计划（2006cB503900）
国家自然科学基金（30471926、30671110）
广西壮族自治区卫生厅项目（G200033）
广西自然科学基金（桂科白9912032、0422012、0447022）
