Xu Jin, Yang Ying-zhong, Tang Feng, Ga Qin, Wuren Tana, Wang Zhan, Ma Lan, Rondina Matthew T, Ge Ri-li
Research Center for High Altitude Medical Sciences, Qinghai University School of Medicine, Qinghai 810001, China; Department of Clinical Medicine, Qinghai University School of Medicine, Qinghai 810001, China.
Research Center for High Altitude Medical Sciences, Qinghai University School of Medicine, Qinghai 810001, China.
Gene. 2015 Jul 25;566(2):257-63. doi: 10.1016/j.gene.2015.04.056. Epub 2015 Apr 23.
Tibetans adapt to high altitude environments through low blood hemoglobin concentrations. Previous work has identified that CYP17A1 and CYP2E1 genes exhibit evidence of local positive selection for this Tibetan high-altitude adaptation. Nevertheless, despite this apparent genetic advantage, some Tibetans still develop high altitude polycythemia (HAPC) yet the reasons for this remain unknown. We sought to determine if polymorphisms in CYP17A1 and CYP2E1 genes were associated with susceptibility to HAPC in Tibetans at the Qinghai-Tibetan Plateau in China. We enrolled 63 Tibetan HAPC patients and 131 healthy, age- and gender-matched control Tibetans. All subjects are from the Yushu area of Qinghai where the altitude is over 3500 m. Three SNPs of the CYP17A1 including rs3781287, rs11191548 and rs1004467, and four SNPs of CYP2E1 gene, including rs1536836, rs3813865, rs3813867 and rs743535, were genotyped by the Sequenom MassARRAY SNP assays. We discovered that SNP rs1004467 of the CYP17A1 gene and SNP rs3813865 of the CYP2E1 gene were significantly associated with HAPC risk. Furthermore, we identified a positive correlation between these two SNPs and plasma hemoglobin levels. Thus, taken together, our study is the first to our knowledge to show that polymorphisms in the rs1004467 SNP of CYP17A1 and rs3813865 SNP of CYP2E1 correlate with susceptibility to HAPC.
藏族人通过低血红蛋白浓度来适应高海拔环境。先前的研究已经确定，CYP17A1和CYP2E1基因表现出对藏族人高海拔适应的局部正选择证据。然而，尽管有这种明显的遗传优势，一些藏族人仍然会患上高原红细胞增多症（HAPC），但其原因尚不清楚。我们试图确定CYP17A1和CYP2E1基因的多态性是否与中国青藏高原藏族人患HAPC的易感性相关。我们招募了63名藏族HAPC患者和131名年龄、性别匹配的健康藏族对照者。所有受试者均来自青海玉树地区，该地区海拔超过3500米。通过Sequenom MassARRAY SNP检测法对CYP17A1的三个单核苷酸多态性（SNP），包括rs3781287、rs11191548和rs1004467，以及CYP2E1基因的四个SNP，包括rs1536836、rs3813865、rs3813867和rs743535进行基因分型。我们发现CYP17A1基因的SNP rs1004467和CYP2E1基因的SNP rs3813865与HAPC风险显著相关。此外，我们还发现这两个SNP与血浆血红蛋白水平呈正相关。因此，据我们所知，我们的研究首次表明，CYP17A1的rs1004467 SNP和CYP2E1的rs3813865 SNP多态性与HAPC易感性相关。
