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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 = 0.9). 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 γ 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.

anthropological science

Native highland and lowland populations differ in .GAMMA.-globin gene promoter polymorphisms related to altered fetal hemoglobin levels and delayed fetal to adult globin switch after birth