中国汉族高原肺水肿易感基因的全基因组关联的研究.pdfVIP

HEREDITAS (Beijing) 2013 11 , 35(11): 1291―1299 ISSN 0253-9772 研究报告 DOI: 10.3724/SP.J.1005.2013.01291 中国汉族高原肺水肿易感基因的全基因组关联研究 杨应忠, 王亚平, 马兰, 杜洋, 格日力 , 810001 高原肺水肿(High-altitude pulmonary edema, HAPE)是一种特发于高原低氧环境的肺水肿, 是遗传和环境 因素共同作用的结果。为了寻找与中国汉族高原肺水肿相关的单核苷酸多态性(Single nucleotide polymorphism, SNP)位点及易感基因, 文章利用Affymetrix SNP Array 6.0 芯片, 对2010 年5 月至2012 年7 月在青海省玉树地 区执行援建任务时来自平原地区的40 例HAPE 患者和33 例健康对照进行全基因组 SNP 分型, 通过PLINK 软 件对芯片结果进行全基因组关联分析(Genome-wide association study, GWAS), 筛选出在病例组和对照组中间有 显著差异(P 10E-7) 的SNP 位点57 个, 通过对57 个SNP 位点附近74 个基因进行GO 与Pathway 富集分析, 发 现这些基因与“前列腺素代谢”、“四烯酸代谢”、“氮代谢”显著相关(adjust P 0.05), 以上代谢过程与HAPE 病理生理机制相关。结果表明, 高原肺水肿受遗传多态性影响, 与多个基因以及位点相关。 高原肺水肿; 单核苷酸多态性; 全基因组关联分析; 易感基因 Genome-wide association study of high-altitude pulmonary edema in Han Chinese YANG Ying-Zhong, WANG Ya-Ping, MA Lan, DU Yang, GE Ri-Li Research Center for High Altitude Medical Sciences, Medical College of Qinghai University , Xining 810001, China Abstract: High-altitude pulmonary edema (HAPE) is a non-cardiogenic pulmonary edema that is always found among unacclimatized persons after rapid ascent to high altitude, and HAPE is caused by the interaction of genetic and environ- mental factors. To screen and analyze the susceptibility genes and single nucleotide polymorphisms (SNPs) of HAPE in Han Chinese, the DNA samples of 40 patients with HAPE and 33 healthy controls, who performed the reconstruction tasks from the plain region in Yushu area of Qinghai province during May of 2010 to July of 2012, were scanned by Affymetrix SNP Array 6.0 Chips in this study. Genome-wide association study (GWAS, by PLINK software) was used to screen the susceptibility genes and geneti