Department of Neurology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan.
College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.
Genes (Basel). 2020 Dec 18;11(12):1514. doi: 10.3390/genes11121514.
Cardiovascular diseases (CVDs) and dementia are the leading causes of disability and mortality. Genetic connections between cardiovascular risk factors and dementia have not been elucidated. We conducted a scoping review and pathway analysis to reveal the genetic associations underlying both CVDs and dementia. In the PubMed database, literature was searched using keywords associated with diabetes mellitus, hypertension, dyslipidemia, white matter hyperintensities, cerebral microbleeds, and covert infarctions. Gene lists were extracted from these publications to identify shared genes and pathways for each group. This included high penetrance genes and single nucleotide polymorphisms (SNPs) identified through genome wide association studies. Most risk SNPs to both diabetes and dementia participate in the phospholipase C enzyme system and the downstream nositol 1,4,5-trisphosphate and diacylglycerol activities. Interestingly, AP-2 (TFAP2) transcription factor family and metabolism of vitamins and cofactors were associated with genetic variants that were shared by white matter hyperintensities and dementia, and by microbleeds and dementia. Variants shared by covert infarctions and dementia were related to VEGF ligand-receptor interactions and anti-inflammatory cytokine pathways. Our review sheds light on future investigations into the causative relationships behind CVDs and dementia, and can be a paradigm of the identification of dementia treatments.
心血管疾病（CVDs）和痴呆症是导致残疾和死亡的主要原因。心血管危险因素与痴呆症之间的遗传联系尚未阐明。我们进行了范围审查和途径分析，以揭示 CVDs 和痴呆症的遗传关联。在 PubMed 数据库中，使用与糖尿病、高血压、血脂异常、脑白质高信号、脑微出血和隐匿性梗死相关的关键词进行文献检索。从这些出版物中提取基因列表，以确定每个组的共享基因和途径。这包括通过全基因组关联研究确定的高外显率基因和单核苷酸多态性（SNP）。大多数与糖尿病和痴呆症相关的风险 SNP 参与磷脂酶 C 酶系统以及下游的肌醇 1,4,5-三磷酸和二酰基甘油活性。有趣的是，AP-2（TFAP2）转录因子家族和维生素及辅因子的代谢与与脑白质高信号和痴呆症、微出血和痴呆症共享的遗传变异有关。与隐匿性梗死和痴呆症共享的变异与 VEGF 配体-受体相互作用和抗炎细胞因子途径有关。我们的综述为未来研究 CVDs 和痴呆症背后的因果关系提供了线索，并可以作为确定痴呆症治疗方法的范例。
