Whole genome association study in high-altitude pulmonary edema

本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。利用400个多态微卫星标记，通过PCR和gene Scan软件对HAPE易感人群和HAPE抗性人群进行病例-对照关联研究。9个标记与HAPE易感性有统计学意义相关，3个标记与HAPE抗性有统计学意义相关。我们还评估了HAPE与组织金属蛋白酶3 （TIMP3）基因的6个单核苷酸多态性（SNP）的相关性，发现其中一个SNP （rs130293）与HAPE易感性显著相关（P < 0.0005）。本研究首次证明了HAPE的发展可能是由多个基因的相互作用决定的，TIMP3可能会影响HAPE的风险。

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.