载脂蛋白 E、载脂蛋白 A7、A2M、BACE1 的常见变异与阿尔茨海默病患者脑脊液生物标志物的相关性：来自 PUMCH 痴呆队列的数据。
Association Between Common Variants of APOE, ABCA7, A2M, BACE1, and Cerebrospinal Fluid Biomarkers in Alzheimer's Disease: Data from the PUMCH Dementia Cohort.
机构信息
Neurology Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Institute of Basic Medical Sciences, Peking Union Medical College, Beijing, China.
出版信息
J Alzheimers Dis. 2022;85(4):1511-1518. doi: 10.3233/JAD-215067.
BACKGROUND
The previous studies have identified several genes in relation to Alzheimer's disease (AD), such as ABCA7, CR1, etc. A few studies have explored the association between the common variants, mainly in the non-coding regions of these genes, and cerebrospinal fluid (CSF) biomarkers. Fewer studies target the variants in the coding regions.
OBJECTIVE
To illustrate the association between the common variants within or adjacent to the coding regions of AD susceptible genes and CSF biomarkers in AD patients.
METHODS
75 sporadic probable AD patients were extracted from the dementia cohort of Peking Union Medical College Hospital. They all had history inquiry, physical examination, blood test, cognitive assessment, brain MRI, CSF testing of Aβ42, 181p-tau, and t-tau, and next-generation DNA sequencing. Sixty-nine common single nucleotide polymorphisms (SNPs) (minor allele frequency > 0.01) within or near the coding region of 13 AD susceptible genes were included in the analysis.
RESULTS
The rs7412-CC (APOE) genotype showed lower CSF Aβ42 level and higher p-tau/Aβ42 ratio than the rs7412-CT genotype. The rs3752246-C (ABCA7) allele correlated with lower CSF Aβ42 level. The alternate alleles of six ABCA7 SNPs were related to lower CSF p-tau, including rs3745842, rs3764648, rs3764652, rs4147930, rs4147934 and rs881768. The rs11609582-TT (A2M) genotype showed higher CSF p-tau than the rs11609582-TA genotype. The p-tau/Aβ42 ratio was higher in the rs490460-TT (BACE1) genotype relative to the rs490460-GT genotype.
CONCLUSION
Some common variants within or near the coding regions of APOE, ABCA7, A2M, and BACE1 are associated with CSF Aβ42, p-tau. or p-tau/Aβ42.
背景
先前的研究已经确定了与阿尔茨海默病（AD）相关的几个基因，如 ABCA7、CR1 等。一些研究探索了这些基因的常见变异体（主要是非编码区域）与脑脊液（CSF）生物标志物之间的关联。针对编码区域中的变异体的研究较少。
目的
说明 AD 易感基因的编码区或其附近的常见变异体与 AD 患者的 CSF 生物标志物之间的关联。
方法
从北京协和医学院医院的痴呆队列中提取了 75 例散发性可能的 AD 患者。他们均接受了病史询问、体格检查、血液检查、认知评估、脑 MRI、CSF 检测 Aβ42、181p-tau 和 t-tau，以及下一代 DNA 测序。分析中包含了 13 个 AD 易感基因的编码区或其附近的 69 个常见单核苷酸多态性（SNP）（次要等位基因频率>0.01）。
结果
与 rs7412-CT 基因型相比，rs7412-CC（APOE）基因型的 CSF Aβ42 水平较低，p-tau/Aβ42 比值较高。ABCA7 基因的 rs3752246-C 等位基因与较低的 CSF Aβ42 水平相关。六个 ABCA7 SNP 的交替等位基因与较低的 CSF p-tau 相关，包括 rs3745842、rs3764648、rs3764652、rs4147930、rs4147934 和 rs881768。与 rs11609582-TA 基因型相比，rs11609582-TT（A2M）基因型的 CSF p-tau 水平较高。与 rs490460-GT 基因型相比，rs490460-TT（BACE1）基因型的 p-tau/Aβ42 比值较高。
结论
APOE、ABCA7、A2M 和 BACE1 的编码区或其附近的一些常见变异体与 CSF Aβ42、p-tau 或 p-tau/Aβ42 相关。
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