EPAS1基因多态性与急性高原病关联性研究

Relationships between EPAS1 gene polymorphisms and acute mountain sickness

目的探讨中国平原汉族人群中EPAS1基因多态性同急性高原病(acute mountain sickness,AMS)易感性的关系。方法采取病例对照研究方法,根据AMS路易斯湖评分系统(LLS)对受试者进行AMS的判定。采用聚合酶链反应-连接酶检测反应方法(PCR-LDR)测定80例AMS患者和86例健康对照组人群EPAS1基因位点rs2044456、rs4953348的基因多态性。结果 AMS组及对照组中基因位点rs2044456、rs4953348均检测出AA、AG、GG基因型,rs2044456位点基因型及等位基因频率组间差异无统计学意义;rs4953348位点AG基因型频率与GG基因型频率相比,组间差异具有统计学意义(OR=0.453,95%CI 0.226～0.908,P=0.026);AMS组A等位基因频数显著低于对照组(25.0%vs 35.5%,OR=0.607,95%CI 0.377～0.975,P=0.039)。分别比较各位点不同基因型心率及血氧饱和度水平,发现该两个位点不同基因型携带者高原血氧饱和度具有统计学差异(P<0.05)。结论位点rs4953348基因多态性与mAMS易感性相关,携带AG基因型的人群患AMS的风险性可能较携带GG基因型人群低,而A等位基因则可能是mAMS的保护性因素;各位点不同基因型均同血氧饱和度有较强关联性(P<0.05)。

Objective To investigate the relationships between single nucleotide polymorphism（SNP） of the EPAS1 gene and the susceptibility of acute mountain sickness（AMS） among Han population in China.Methods A case-control association study was conducted.Eighty male Chinese patients with AMS,defined according to the Lake Louise acute mountain sickness scoring system（LLS）,were compared with 86 Chinese men free of symptoms of AMS.The polymerase chain reaction-ligase detection reaction（PCR-LDR） technique was used to detect the SNPs of rs2044456 and rs4953348 in EPAS1 gene.Results Genotypes of the SNP rs2044456,rs4953348 AA,AG and GG were detected in both AMS and control groups.The genotype and allele frequencies of the rs2044456 showed no significant difference between the two groups;but significant difference was found in the AG and GG genotype distribution of rs4953348 between them（OR=0.453,95%CI 0.226-0.908,P=0.026）.The frequency of allele A in the AMS group was significantly lower than that in the control group（25.0%vs 35.5%,OR=0.607,95%CI 0.377-0.975,P=0.039）.There was also statistically significant difference in the level of blood oxygen saturation（SaO2）at high altitude between different genotypes of rs2044456 and rs4953348（P0.05）,but not in the level of heart rate.Conclusion The SNP of rs4953348 in EPAS1 gene may be associated with the development of AMS amog Chinese Han population,and individuals with the genotype AG may be less vulnerable to AMS than those who carry the genotype of GG.A allele may serve as the protective factor of AMS.The genotypes of both rs2044456 and rs4953348 may be associated with the level of SaO2（P〈0.05）.