EPAS1基因不同单体型与高原低氧适应的相关性研究  

Study on the relationship between EPAS1 gene haplotype and high altitude hypoxia adaptation

作　　者：李翠莹[1] 李小薇[1] 刘娟[1] 雷慧芬[1] 李景琦[1] 熊梅[1] 甘新宇[2] 肖洁[2] 黄菲[2] 于丽君[2] 

机构地区：[1]空军总医院输血科,北京100142 [2]成都军区总医院输血科

出　　处：《中国输血杂志》2017年第8期863-866,共4页Chinese Journal of Blood Transfusion

基　　金：全军后勤科研重大专项子项(AWS13J004)

摘　　要：目的探讨EPAS1基因突变位点在世居高原和世居平原人群中的差异,并进一步分析其与世居平原人群进入高原后低氧适应的相关性。方法选择西藏藏族50名和平原汉族100名作为研究对象,提取DNA,应用聚合酶链式反应(PCR)技术结合测序进行EPAS1基因2个单核苷酸多态位点(SNPs)rs13419896,rs1868092检测。选择50名汉族进入高原前后血红蛋白(Hb)差值≥35 g/L、红细胞计数(RBC)差值≥1×1012/L和红细胞比容(Hct)差值≥0.1共20名作为观察组,其余30名作为对照组,分析2组之间携带不同单体型者血液学指标变化。结果rs13419896位点A等位基因频率在藏族和汉族中分别为88.0%和27.0%,rs1868092位点A等位基因频率在藏族和汉族中分别为80.0%和10.0%,两组比较均具有统计学差异(P<0.000)。SHEsis构建单体型结果发现,观察组中rs13419896和rs1868092单体型(A-A)显著低于对照组(P<0.05,OR=0.032,95%CI=0.003-0.382)。结论 EPAS1基因rs13419896(G>A)和rs1868092(G>A)位点突变与西藏藏族适应高原低氧环境存在相关性。汉族人群进入高原后,携带EPAS1单体型rs13419896和rs1868092(A-A)既能更好地适应高原低氧环境,又可以降低自身血液黏滞度,利于高原低氧习服。Objective This study aims to explore the difference in EPAS1 gene variation between the Tibetans who are conditioned to live at a higher altitude and individuals conditioned to a normal altitude and oxygen level. We also focus to further analyze the correlation between the EPAS1 gene mutation and hypoxic adaptation for people living at plain areas upon entering hypoxic environment with high altitudes. Methods The blood samples were chosen from 50 Tibetans at Tibet high altitude and 100 Han people in Chengdu at 500 m above see level. Genomic DNA was extracted from these blood samples. The single nueleotide polymorphisms （SNPs） of EPAS1 gene were screened by polymerase chain reaction （PCR） and sequencing. Threshold values were drawn in hemoglobin （Hb） at ≥ 35g / L, red blood cell （RBC） count at ≥ l×10^12/L and hematocrit （Hct） at I〉 0. 1 for the 50 Han people entering higher altitudes, yielding a experiment group of 20 cases and the rest 30 samples functioned as the control group. We then analyzed hematological changes in patients with different haplotypes. Results The A allele frequency of EPAS1 gene rs13419896 in Tibetans and Han was 88. 0% and 27. 0%, respectively while the A allele frequency of rs1868092 was 80. 0% and 10.0%. These two groups presented significant differences （P〈0. 000）. For SHEsis constructed haplotypes, the results demonstrated that the haplotypes A-A of rs13419896 and rs1868092 in the experiment group were significantly lower than in the control group （P〈0. 05, OR= 0. 032, 95% CI= 0. 003-0. 382）. Conclu- sion The variation of EPAS1 gene rs13419896 （G〉A） and rs1868092 （G〉A） were associated with hypoxic adaptation in high altitude in Tibetans. Upon entering higher ahitudes, the Han people carrying the EPAS1 haplotype rs13419896 and rs 1868092 （A-A） better adapted to the hypoxia environment with reduced blood viscosity, which is beneficial to plateau hy- poxia acclimatization.

关 键 词：EPAS1基因 单核苷酸多态性 血液学指标 高原低氧适应 

分 类 号：R457.11[医药卫生—治疗学] R135.6[医药卫生—临床医学]