Whole genome association study in high-altitude pulmonary edema

这项研究的目的是试图确定可能与高原肺水肿(HAPE)发展相关的候选人类基因。应用聚合酶链式反应和基因扫描软件对HAPE易感和抗HAPE的400个微卫星标记进行病例-对照关联研究。9个标记与HAPE易感性显著相关，3个标记与HAPE抗性显著相关。我们还评估了HAPE与金属蛋白酶组织抑制因子3(TIMP3)基因的6个单核苷酸多态(SNP)的相关性，发现其中一个SNP(Rs130293)与HAPE的易感性显著相关(P&lt；0.0005)。本研究首次证明HAPE的发生可能由多个基因的相互作用决定，TIMP3可能影响HAPE的发病风险。

The aim of this study is attempt to identify the candidate human genes those might associate with the development of high-altitude pulmonary edema (HAPE). A case-control association study was performed using 400 polymorphic microsatellite markers by PCR and sequenced byGene Scan software in HAPE susceptible subjects and HAPE resistant subjects. Nine markers showed statistically significant associations with the susceptibility to HAPE, and three markers showed significant associations with the resistance to HAPE. We also evaluated the association of HAPE with six single nucleotide polymorphisms (SNPs) in tissue inhibitor of metalloproteinase 3 (TIMP3) gene, and found that one SNP (rs130293) was significantly associated with the HAPE susceptibility (P < 0.0005). This study provides the first evidence that the development of HAPE may be determined by the interaction of multiply genes and TIMP3 may influence the risk for HAPE.