世居不同高海拔藏族EGLN1多态与海拔水平的关联研究

Association Study on EGLN1 SNPs and Different Levels of High Altitude Among Native Tibetans

在世居高原藏族人群中探索Egl-9家族同源物1基因(EGLN1)遗传变异与不同的高海拔水平及生理表型的关联.募集178例居住于海拔2 700m个体(LHA组),245例3 700m个体(MHA组),179例4 700m个体(HHA组).分型EGLN1 4个连锁的单核苷酸多态(SNP)rs2790882,rs480902,rs2486736和rs2739513,并进行它们与不同高海拔、肺功能、血氧饱和度(SaO2)的关联分析.4个SNPs的常见等位基因频率均随LHA、MHA、HHA递增(所有P<0.05);其单倍域中常见CTCC单倍型频率从LHA的52.5%增加至MHA的59.8%及HHA的62.3%(P=0.001 2).4个SNPs在HHA组SaO2水平随少见纯合子、杂合子和常见纯合子均递增(所有P<0.05),且CT/CC携带者的SaO2水平比少见单倍型TC/TT升高了1.6%(P=0.001 5).高原藏族人从海拔2 700m升高到3 700m及4 700mEGLN1基因受到了选择.在极高海拔时,EGLN1基因变异影响SaO2水平.

To investigate the associations of Egl nine homolog 1 （EGLN1） variants with different levels of high altitude and physiological traits among native Tibetans. Overall 178 Tibetan subjects living at 2 700 m （low level of high altitude, group LHA）, 245 subjects at 3 700 m （middle level of high altitude, group MHA） and 179 subjects at 4700m （high level of high altitude, group HHA） were recruited, Four EGLN1 single nucleotide polymorphisms （SNPs） in high linkage disequilibrium （rs2790882, rs480902, rs2486736 and rs2739513） were genotyped and were associated with levels of high altitude, respiratory traits and SaO2. we found an increasing trend of major allele frequencies of all 4 SNPs from LHA, MHA to HHA （all P%0. 05）. The major haplotype CTCC increases from LHA （52. 5%）, MHA （59. 8%） to HHA （62. 3%） （P=0. 001 2）. We also found an increasing levels of SaO2 from the major homozygotes, heterozygotes to minor homozygotes of the four SNPs （all P〈0. 05）. In addition haplotype CTCC increases the level of SaO2 by 1.6% in HHA group, compared with minor TCTT haplotype （P=0. 001 5）. The increase of living altitudes from 2 700 m, 3 700 m to 4 700 m imposed a selective effect on EGLN1 alleles among high altitude native Tibetans. EGLNi genetic variations were associated with SaO2 level at an extremelylhigh altitude.