Chen Yi-Chun, Liu Yu-Li, Tsai Shih-Jen, Kuo Po-Hsiu, Huang Shih-Sin, Lee Yun-Shien
Department of Neurology, Chang Gung Memorial Hospital Linkou Medical Center and College of Medicine, Chang-Gung University, No.5, Fuxing St., Guishan Township, Taoyuan County 333, Taiwan.
Dementia Center, Chang Gung Memorial Hospital Linkou Medical Center, Taoyuan County 333, Taiwan.
J Clin Med. 2019 Jul 29;8(8):1124. doi: 10.3390/jcm8081124.
Hypotension can affect cerebral perfusion and worsen cognitive outcomes. The prevalence of low blood pressure (BP) rises with increasing age. To our knowledge, no study has examined the genetic biomarkers for hypotension-related cognitive impairment (CI) yet. Utilizing the population-based genome-wide study of the Taiwan Biobank containing the data of 2533 healthy aging subjects, we found after adjustments for age, sex, education years, and principal components at a suggestive level of 1 × 10 that minor alleles of (rs13388459, rs1075716, rs62171995, rs17406146, rs2077823, and rs62170897), ( (rs10521467), and the intergenic variation rs117129097 (the nearby gene: ) are risk factors for CI in hypotensive subjects. Except for rs117129097, these single nucleotide polymorphisms (SNPs) were not markers per se for CI or for BP regulation. However, we found a suggestive interaction effect between each of the eight SNPs and hypotension on CI risk. In the hypotensive participants, those carrying minor alleles were associated with a higher incidence of CI in an additive manner than were those carrying major alleles (2 × 10 to 9 × 10). Intensive BP lowering in elderly patients carrying a minor allele of the eight identified SNPs should raise cautions to prevent a potential treatment-induced neurodegeneration.
低血压会影响脑灌注并恶化认知结局。低血压的患病率随年龄增长而上升。据我们所知，尚无研究探讨与低血压相关的认知障碍（CI）的遗传生物标志物。利用台湾生物银行基于人群的全基因组研究，该研究包含2533名健康老年人的数据，我们发现在对年龄、性别、受教育年限和主成分进行调整后，在1×10的提示水平下，（rs13388459、rs1075716、rs62171995、rs17406146、rs2077823和rs62170897）、（（rs10521467）以及基因间变异rs117129097（附近基因：）的次要等位基因是低血压患者CI的危险因素。除rs117129097外，这些单核苷酸多态性（SNP）本身并非CI或血压调节的标志物。然而，我们发现这八个SNP中的每一个与低血压之间对CI风险存在提示性的交互作用。在低血压参与者中，携带次要等位基因的人比携带主要等位基因的人以累加方式发生CI的发生率更高（2×10至9×10）。对携带八个已鉴定SNP次要等位基因的老年患者进行强化降压时应谨慎，以防止潜在的治疗诱导性神经变性。
