Hong Kyung-Won, Kim Sung Soo, Kim Yeonjung
Division of Epidemiology and Health Index, Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongwon 363-951, Korea.
Genomics Inform. 2013 Sep;11(3):129-34. doi: 10.5808/GI.2013.11.3.129. Epub 2013 Sep 30.
Orthostatic hypotension (OH) is defined by a 20-mm Hg difference of systolic blood pressure (dtSBP) and/or a 10-mm Hg difference of diastolic blood pressure (dtDBP) between supine and standing, and OH is associated with a failure of the cardiovascular reflex to maintain blood pressure on standing from a supine position. To understand the underlying genetic factors for OH traits (OH, dtSBP, and dtDBP), genome-wide association studies (GWASs) using 333,651 single nucleotide polymorphisms (SNPs) were conducted separately for two population-based cohorts, Ansung (n = 3,173) and Ansan (n = 3,255). We identified 8 SNPs (5 SNPs for dtSBP and 3 SNPs for dtDBP) that were repeatedly associated in both the Ansung and Ansan cohorts and had p-values of <1 × 10(-5) in the meta-analysis. Unfortunately, the SNPs of the OH case control GWAS did not pass our p-value criteria. Four of 8 SNPs were located in the intergenic region of chromosome 2, and the nearest gene (CTNNA2) was located at 1 Mb of distance. CTNNA2 is a linker between cadherin adhesion receptors and the actin cytoskeleton and is essential for stabilizing dendritic spines in rodent hippocampal neurons. Although there is no report about the function in blood pressure regulation, hippocampal neurons interact primarily with the autonomic nervous system and might be related to OH. The remaining SNPs, rs7098785 of dtSBP trait and rs6892553, rs16887217, and rs4959677 of dtDBP trait were located in the PIK3AP1 intron, ACTBL2-3' flanking, STAR intron, and intergenic region, respectively, but there was no clear functional link to blood pressure regulation.
直立性低血压（OH）定义为仰卧位和站立位之间收缩压相差20 mmHg（dtSBP）和/或舒张压相差10 mmHg（dtDBP），且OH与心血管反射无法在从仰卧位站立时维持血压有关。为了解OH特征（OH、dtSBP和dtDBP）的潜在遗传因素，分别对两个基于人群的队列（安城队列，n = 3173；安山队列，n = 3255）进行了使用333,651个单核苷酸多态性（SNP）的全基因组关联研究（GWAS）。我们鉴定出8个SNP（5个与dtSBP相关，3个与dtDBP相关）在安城和安山队列中均反复出现关联，且在荟萃分析中的p值<1×10⁻⁵。遗憾的是，OH病例对照GWAS的SNP未通过我们的p值标准。8个SNP中的4个位于2号染色体的基因间区域，最近的基因（CTNNA2）位于距离1 Mb处。CTNNA2是钙黏蛋白黏附受体与肌动蛋白细胞骨架之间的连接蛋白，对稳定啮齿动物海马神经元中的树突棘至关重要。尽管尚无关于其在血压调节中功能的报道，但海马神经元主要与自主神经系统相互作用，可能与OH有关。其余SNP，dtSBP特征的rs7098785以及dtDBP特征的rs6892553、rs16887217和rs4959677分别位于PIK3AP1内含子、ACTBL2的3'侧翼、STAR内含子和基因间区域，但与血压调节没有明确的功能联系。
