Heinrich Erica C, Wu Lu, Lawrence Elijah S, Cole Amy M, Anza-Ramirez Cecilia, Villafuerte Francisco C, Simonson Tatum S
Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla, California.
Department of Molecular & Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
Ann Hum Genet. 2019 May;83(3):171-176. doi: 10.1111/ahg.12299. Epub 2019 Feb 4.
EGLN1 encodes the hypoxia-inducible factor (HIF) pathway prolyl hydroxylase 2 (PHD2) that serves as an oxygen-sensitive regulator of HIF activity. The EGLN1 locus exhibits a signature of positive selection in Tibetan and Andean populations and is associated with hemoglobin concentration in Tibetans. Recent reports provide evidence for functional roles of protein-coding variants within the first exon of EGLN1 (rs186996510, rs12097901) that are linked to an adaptive signal in Tibetans, yet whether these same variants are present and contribute to adaptation in Andean highlanders is unknown. We determined the frequencies of these adaptive Tibetan alleles in Quechua Andeans resident at high altitude (4,350 m) in addition to individuals of Nepali ancestry resident at sea level. The rs186996510 C (minor) allele previously found at high frequency in Tibetans is absent in Andean (G: 100%) and rare among Nepali (C: 11.8%, G: 88.2%) cohorts. The minor G allele of rs12097901 is found at similarly low frequencies in Andeans (G: 12.7%, C: 87.3%) and Nepalis (G: 23.5%, C: 76.5%) compared to Tibetans. These results suggest that adaptation involving EGLN1 in Andeans involves different mechanisms than those described in Tibetans. The precise Andean adaptive variants remain to be determined.
EGLN1基因编码缺氧诱导因子（HIF）途径脯氨酰羟化酶2（PHD2），它作为HIF活性的氧敏感调节因子。EGLN1基因座在藏族和安第斯人群中表现出正选择特征，并且与藏族人的血红蛋白浓度相关。最近的报告提供了证据，证明EGLN1第一个外显子内的蛋白质编码变体（rs186996510、rs12097901）具有功能作用，这些变体与藏族人的适应性信号相关，但尚不清楚这些相同的变体是否存在于安第斯高地人中并促成了他们的适应性变化。除了居住在海平面的尼泊尔裔个体外，我们还测定了居住在高海拔（4350米）的克丘亚族安第斯人中这些适应性藏族等位基因的频率。先前在藏族人中高频发现的rs186996510 C（次要）等位基因在安第斯人群中不存在（G：100%），在尼泊尔人群中也很罕见（C：11.8%，G：88.2%）。与藏族人相比，rs12097901的次要G等位基因在安第斯人群（G：12.7%，C：87.3%）和尼泊尔人群（G：23.5%，C：76.5%）中的频率同样较低。这些结果表明，安第斯人群中涉及EGLN1的适应性变化所涉及的机制与藏族人群中描述的机制不同。安第斯人群确切的适应性变体仍有待确定。
