Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
J Physiol Sci. 2013 May;63(3):183-93. doi: 10.1007/s12576-013-0257-8. Epub 2013 Apr 4.
Mountain sickness (MS) occurs among humans visiting or inhabiting high altitude environments. We conducted genetic analyses of seven single nucleotide polymorphisms (SNPs) in the promoter region of VEGFA gene for lowland (Han) and highland (Tibetan) Chinese. The seven SNPs were evaluated in Han and Tibetan patients with acute (A) and chronic (C) MS. We compared 64 patients with AMS with 64 Han unaffected with MS, as well as 48 CMS patients with 32 unaffected Tibetans. The SNPs studied are rs699947, rs34357231, rs79469752, rs13207351, rs28357093, rs1570360, and rs2010963 which are found in the promoter ranging from -2,578 to -634 bp from the transcriptional start site (TSS), respectively. Direct sequencing was used to identify individual genotypes for these SNPs. Arterial oxygen saturation of hemoglobin (SaO2) was found to be significantly associated with the rs699947, rs34357231, rs13207351, and rs1570360 SNPs in Han patients with AMS, while the rs2010963 SNP was found to approach significance in the AMS study group, but found to be significantly associated in the normal Tibetan study group. The Han and Tibetan control groups were found to diverge significantly for the rs28357093 and rs2010963 SNPs, as measured by genetic distances of 0.073 and 0.054, respectively. All the SNPs are found in transcriptional factor binding sites (TFBS), and their possible role in gene regulation was evaluated with regard to MS. MS was found to be significantly associated with these SNPs compared with their Han and Tibetan control groups, indicating that these nucleotide substitutions result in TFBS changes which apparently have a physiological effect on the development of high altitude sickness.
高山病（MS）发生在人类访问或居住在高海拔环境中。我们对 VEGF 基因启动子区域的七个单核苷酸多态性（SNP）进行了遗传分析，这些 SNP 存在于低地（汉族）和高地（藏族）中国人中。在汉族和藏族的急性（A）和慢性（C）MS 患者中评估了这七个 SNP。我们将 64 例急性高原病（AMS）患者与 64 例未患 MS 的汉族患者进行了比较，将 48 例慢性高原病（CMS）患者与 32 例未患 MS 的藏族患者进行了比较。所研究的 SNP 是 rs699947、rs34357231、rs79469752、rs13207351、rs28357093、rs1570360 和 rs2010963，它们分别位于转录起始位点（TSS）上游的-2578bp 到-634bp 处。直接测序用于确定这些 SNP 的个体基因型。研究发现，汉族 AMS 患者的血红蛋白动脉血氧饱和度（SaO2）与 rs699947、rs34357231、rs13207351 和 rs1570360 显著相关，而 rs2010963 SNP 在 AMS 研究组中接近显著，但在正常藏族研究组中则显著相关。汉族和藏族对照组在 rs28357093 和 rs2010963 SNP 上的差异非常显著，遗传距离分别为 0.073 和 0.054。所有 SNP 都存在于转录因子结合位点（TFBS）中，我们评估了它们在 MS 基因调控中的可能作用。与汉族和藏族对照组相比，MS 与这些 SNP 显著相关，表明这些核苷酸替换导致 TFBS 变化，这显然对高原病的发展有生理影响。
