Native highland and lowland populations differ in γ-globin gene promoter polymorphisms related to altered fetal hemoglobin levels and delayed fetal to adult globin switch after birth
Native highland and lowland populations differ in γ-globin gene promoter polymorphisms related to altered fetal hemoglobin levels and delayed fetal to adult globin switch after birth
复制标题
DOI：
10.1537/ase.090402
复制
发表时间：
2010-04-01
影响因子：
0.7
通讯作者：
Dittmar, Manuela
中科院分区：
文献类型：
--
作者：
Rottgardt, Inken;Rothhammer, Francisco;Dittmar, Manuela
高海拔地区较低的氧分压产生了强大的选择压力。由于缺氧对胎儿最为严重，胎儿血红蛋白基因（HBG1、HBG2）是适应高海拔的遗传适应候选基因。本研究的目的是比较这些基因的启动子多态性在高原和低地人群之间的差异。对50名智利安第斯山脉的原住民高原居民和50名欧洲血统的低地居民的HBG1和HBG2基因启动子进行了测序。在HBG1启动子中，4个碱基对的AGCA缺失在高原居民中出现的频率低于低地居民（10%对24%，P = 0.014）。在HBG2启动子中，常见的 -158 C>T多态性的T等位基因频率在高原居民中比低地居民降低（8%对34%，P = 0.000009）。对这两个标记的联合分析表明，携带AGCA缺失的高原居民中没有人携带HBG2 T等位基因，而低地居民中有43%（P = 0.030）。由于AGCA缺失与胎儿γ珠蛋白链表达降低有关，它可能会影响高海拔地区胎儿的氧气供应。AGCA缺失和HBG2 -158 T等位基因都与出生后胎儿向成人珠蛋白转换延迟有关，导致成人血红蛋白产生延迟，从而可能影响高海拔地区婴儿的氧气供应。
Lowered partial oxygen pressure at high altitude exerts a strong selection pressure. Since hypoxia is most serious for the fetus, fetal hemoglobin genes (HBG1, HBG2) are candidates for genetic adaptation to high altitude. The aim of this study was to compare promoter polymorphisms of these genes for differences between highland and lowland populations. In 50 native highlanders of the Chilean Andes and 50 lowlanders of European ancestry, the promoters of HBG1 and HBG2 genes were sequenced. In the HBG1 promoter, the 4-basepair AGCA deletion was less frequently present in highlanders than in lowlanders (10% vs. 24%, P = 0.014). In the HBG2 promoter, the frequency of the T allele of the common -158 C > T polymorphism was decreased in highlanders, compared with lowlanders (8% vs. 34%, P=0.000009). A combined analysis of both markers showed that none of the highlanders with the AGCA deletion carried the HBG2 T allele, in contrast to 43% of lowlanders (P=0.030). Since the AGCA deletion is associated with diminished expression of fetal gamma globin chains, it might affect fetal oxygen supply at high altitude. Both the AGCA deletion and the HBG2 158 T allele are associated with a delayed fetal to adult globin switch after birth, resulting in a delayed production of adult hemoglobin, thereby possibly affecting the oxygen supply of infants at high altitude.