Yan Huimin, Liu Minglei, Gao Yuan, Yuan Yanpeng, Liu Xiaojing, Wang Yangyang, Li Lanjun, Wang Qingzhi, Wang Yanlin, Shi Changhe, Xu Yuming, Yang Jing
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
NHC Key Laboratory of Prevention and Treatment of Cerebrovascular Disease, Zhengzhou, Henan, China.
Front Neurol. 2024 Jan 31;15:1326692. doi: 10.3389/fneur.2024.1326692. eCollection 2024.
Overwhelming evidence points to that genetic factors contributing to the development of Alzheimer's disease (AD) and Parkinson's disease (PD). Genome-Wide Association Study (GWAS) has come a long way in the last decade. So far, a large number of GWAS studies have been published on neurological diseases and many other diseases, providing us with a wealth of genetic information and unique biological insights.
Genomic DNA was extracted from both patients' and controls' peripheral blood samples utilizing the Blood Genome Extraction Kit. Single nucleotide polymorphisms (SNPs) were genotyped employing the enhanced multiple ligase detection reaction (iMLDR) technology.
A case-control study was conducted, involving 211 AD patients, 508 PD patients (including 117 with dementia), and 412 healthy individuals. Age and sex stratification analysis revealed that rs871269/ was associated with LOAD ( = 0.035), and rs5011436/ was associated with AD in males ( = 0.044) in the genotype model. In the allele model, rs871269/ was found to be associated with PD in the Chinese Han population ( = 0.0035, OR 0.741, 95% CI 0.559-0.983), and rs708382/ was identified as a risk factor for Parkinson's disease dementia (PDD) in the Chinese Han population ( = 0.004, odds ratio (OR) 0.354, 95% confidence interval (CI) 0.171-0.733). However, no significant associations with AD or PD were observed for the remaining four loci (rs113020870/, rs6891966/, rs2452170/, rs1761461/) in terms of allele or genotype frequencies.
This study identifies rs871269/ as a potential risk factor for both LOAD and PD, rs708382/ as a risk factor for PDD, and rs5011436/ as associated with AD in males when stratified by age.
大量证据表明遗传因素在阿尔茨海默病（AD）和帕金森病（PD）的发病过程中起作用。在过去十年中，全基因组关联研究（GWAS）取得了长足进展。到目前为止，已经发表了大量关于神经疾病和许多其他疾病的GWAS研究，为我们提供了丰富的遗传信息和独特的生物学见解。
使用血液基因组提取试剂盒从患者和对照的外周血样本中提取基因组DNA。采用增强型多重连接检测反应（iMLDR）技术对单核苷酸多态性（SNP）进行基因分型。
进行了一项病例对照研究，纳入211例AD患者、508例PD患者（包括117例患有痴呆症的患者）和412名健康个体。年龄和性别分层分析显示，在基因型模型中，rs871269/与晚发性阿尔茨海默病（LOAD）相关（P = 0.035），rs5011436/在男性中与AD相关（P = 0.044）。在等位基因模型中，发现rs871269/在中国汉族人群中与PD相关（P = 0.0035，OR 0.741，95%CI 0.559 - 0.983），rs708382/被确定为中国汉族人群中帕金森病痴呆（PDD）的一个危险因素（P = 0.004，优势比（OR）0.354，95%置信区间（CI）0.171 - 0.733）。然而，就等位基因或基因型频率而言，其余四个位点（rs113020870/、rs6891966/、rs2452170/、rs1761461/）与AD或PD均未观察到显著关联。
本研究确定rs871269/为LOAD和PD的潜在危险因素，rs708382/为PDD的危险因素，rs5011436/在按年龄分层时与男性AD相关。
