热休克蛋白70基因 rs1008438多态性与高原肺水肿的相关性

目的：探讨热休克蛋白（HSP）70基因启动子区 rs1008438位点单核苷酸多态性（SNP）与高原肺水肿（HAPE）之间的关系。方法采用PCR‐DNA直接测序法检测100例HAPE组、200例健康对照组个体基因组rs1008438位点的基因分布，分析不同基因型与HAPE的关系；运用ELISA法检测不同基因型HAPE组和健康对照组白细胞细胞质和细胞核HSP70蛋白含量变化；应用蛋白质芯片技术和 EVIDENCE180全自动芯片仪分析 TNF‐α、IL‐1β、IL‐6表达水平。结果 HAPE组，健康对照组rs1008438的TT、GT、GG的基因型频率分别是76．0％、20．0％、4．0％，93．0％、6．5％、0．5％。统计处理显示，HAPE组TT基因型频率明显低于健康对照组（P＜0．05）；GT、GG基因型患 HAPE的危险性是 TT基因型的4．195倍，G等位基因相对 T等位基因也能明显增加 HAPE的发病风险（OR＝4．178）；ELISA检测结果显示，不同基因型 HAPE组 HSP70含量均高于健康对照组，且HSP70细胞核／细胞质比值TT基因型高于GT／GG基因型；蛋白质芯片检测表明，HAPE组血清中的TNF‐α、IL‐1β、IL‐6表达水平均明显高于健康对照组。结论 rs1008438位点多态性与 HAPE易感性相关，这种相关性可能是由于突变型在基因转录水平通过影响启动子活性而增强HSP70表达，从而导致HAPE的发生。

The relationship between rs1008438 polymorphism of HSP70 gene and high altitude pulmonary edema

Objective To investigate the relationship between the single nucleotide polymorphisms (SNP) of rs1008438 in HSP70 promoter and the susceptibility of high altitude pulmonary edema (HAPE) .Methods The PCR‐DNA sequencing method was used to analyze gene distribution of rs1008438 in 100 HAPE patients and 200 healthy people ,and the relationship between dif‐ferent genotypes and HAPE was evaluated .Meanwhile ,HSP70 protein in cytoplasm and nuclei of white blood cells were detected by ELISA in patientgroup and healthy group .TNF‐α,IL‐1β and IL‐6 levels were analyzed by protein chip technology and EVI‐DENCE180 automatic chip reader .Results The TT ,GT ,and GG genetype frequencies of rs1008438 in HAPE patients and healthy controls were 76 .0% ,20 .0% ,4 .0% ,and 93 .0% ,6 .5% ,0 .5% ,respectively .The TT genetype frequency in HAPE patients was significantly lower than that in healthy control(P<0 .05) .The HAPE incidence rate in GT/GG genetype was 4 .195 times higher than that in TT genetype ,and the allele G can also significantly increase the prevalence of HAPE compared to T allele (OR=4 .178) .ELISA showed that HSP70 were higher in HAPE group of all genotypes than those in healthy control of the same geno‐type .And the nuclei/cytoplasm ratio of HSP70 in TT genotype was higher than that in GT/GG genotype .Protein chip showed that the levels of TNF α,IL‐1β,and IL‐6 in HAPE group were significantly higher than those in healthy control .Conclusion The poly‐morphism of rs1008438 is related to susceptibility of HAPE .Mutate genetype may change the promoter activity and increase the ex‐pression of HSP70 ,which induced HAPE .