Abstract：
Despite the similar clinical and pathological features between Niemann-Pick type C (NPC) disease and Alzheimer\'s disease (AD), few studies have investigated the role of NPC genes in AD. To elucidate the role of NPC genes in AD, we sequenced NPC1 and NPC2 in 1192 AD patients and 2412 controls. Variants were divided into common variants and rare variants according to minor allele frequency (MAF). Common variant (MAF≥0.01) based association analysis was conducted by PLINK 1.9. Gene-based aggregation testing of rare variants was performed by Sequence Kernel Association Test-Optimal (SKAT-O test), respectively. Age at onset (AAO) and mini-mental state examination (MMSE) association studies were also performed with PLINK 1.9. Six common variants were identified and exhibited no association with AD. Gene-based aggregation testing revealed that both NPC1 and NPC2 were not associated with AD risk. Additionally, AAO and MMSE association studies revealed that no common variants were linked with AD endophenotypes. Taken together, our study indicated that NPC1 and NPC2 may not be implicated in AD pathogenesis in the Chinese population.
摘要：
尽管Niemann-PickC型（NPC）疾病和阿尔茨海默病（AD）之间具有相似的临床和病理特征，很少有研究探讨NPC基因在AD中的作用。阐明NPC基因在AD中的作用,我们对1192例AD患者和2412例对照者的NPC1和NPC2进行了测序。根据次要等位基因频率(MAF)将变体分为常见变体和罕见变体。PLINK1.9进行了基于常见变异（MAF≥0.01）的关联分析。通过序列核关联测试-最佳（SKAT-O测试）进行罕见变异的基于基因的聚集测试，分别。还使用PLINK1.9进行了发病年龄（AAO）和小型精神状态检查（MMSE）关联研究。鉴定了6种常见变体,并且表现出与AD无关联。基于基因的聚集检测显示，NPC1和NPC2均与AD风险无关。此外,AAO和MMSE关联研究显示，没有常见变异与AD内表型相关。一起来看,我们的研究表明，NPC1和NPC2可能与中国人群的AD发病无关。
