EPAS1 and EGLN1 associations with high altitude sickness in Han and Tibetan Chinese at the Qinghai–Tibetan Plateau

Buroker, Norman E.; Xue, Ning; Zhou, Zhao Nian; Li, Kui; Cen, Wei; Wu, Xiu Feng; Zhu, Wei; Scott, C. Ronald; Chen, Shi Han

doi:10.1016/j.bcmd.2012.04.004

Cited by 58 publications

(78 citation statements)

References 36 publications

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“…The people from the control group had lived at the 3600 M altitude for at least six months prior to being sampled. These sampling procedures have been previously described [8][9][10]31].…”

Section: Samplingmentioning

confidence: 99%

“…The Vector NTI Advance 11 computer program from Invitrogen, Carlsbad, CA, was used to develop the primers for genotyping each SNP. The genotyping methods and genotyping for each SNP have been previously outlined and reported [8][9][10]31]. The SNPs and genes used in the present study are found in (Table 1).…”

Section: Genotypingmentioning

confidence: 99%

“…The illness will resolve itself if no additional altitude is attempted; however, in some cases the descent to a lower altitude is necessary in order to reverse the condition. The precise pathogenesis of AMS is not well understood, but hypoxia is considered to be the major factor [4][5][6][7], which raises the question of why some individuals are susceptible to the sickness while others are not, under the same high altitude environment.In an effort to provide in cite into this question, we have previously published on known genetic associations of simple nucleotide polymorphisms (SNPs) with high altitude sickness [8][9][10][11]. In the present study, we examine the interaction of seventeen SNPs in nine genes [8][9][10][11] with regard to AMS and the effect these SNPs have on potential changes in transcriptional factor binding sites (TFBS).…”

Section: Introductionmentioning

confidence: 99%

“…Hypoxia causes an inactivation of the EGLN1 gene thereby increasing HIF activity that induces the expression of genes which mediates the adaptive responses through glycolytic enzymes, hemeoxygenase, vascular endothelial growth factor and erythropoietin [19]. The two EGLN1 SNPs (rs480902 and rs516651) included in the study are located in intron 2 of EGLN1 have been associated with high altitude adaptation in human populations [10,[19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

“…Two genes from the hypoxia-inducible factor (HIF) oxygen signaling pathwayare included in the study [10]. The endothetal Per-ArntSim (PAS) domain protein 1 (EPAS1) gene, which encodes hypoxiainducible-factor-2 alpha (HIF2A) a transcription factor that responses to hypoxia conditions.…”

Section: Introductionmentioning

confidence: 99%

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SNPs, Linkage Disequilibrium and Transcriptional Factor Binding Sites Associated with Acute Mountain Sickness among Han Chinese at the Qinghai-Tibetan Plateau

Buroker¹,

Xue²

2015

J Clin Med Genomics

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Acute mountain sickness (AMS) occurs in up to 50% of individuals ascending to high altitudes greater than 2600 meters. An AMS Han Chinese and a normal Han group were compared for 17 simple nucleotide polymorphisms (SNPs) within 9 genes that have been associated with AMS. The SNPs were analyzed with respect to linkage disequilibrium (LD) between intra-and intergenic SNP alleles and alterations in transcriptional factor binding sites (TFBS). Included in the study was the angiotensin-converting enzyme (ACE) (rs4340), the angiotensinogen (AGT) (rs699) and the angotensin II type 1 receptor (AGTR1) (rs5186) SNPs from the renin-angiotension system (RAS) as well as the GNB3 (rs2071057) SNP from G-protein signaling and a LDL apolipoprotein B (APOB) (rs693) SNP. The endothetal Per-Arnt-Sim (PAS) domain protein 1 (EPAS1) SNP and two egl nine homolog 1 (EGLN1) SNPS (rs480902 and rs516651) from the hypoxia-inducible factor (HIF) oxygen signaling pathway were included. SNPs analyzed in the vascular endothelial growth factor (VEGF) signaling pathway are the v-akt murine thymoma viral oncogene homolog 3 (AKT3) (rs4590656 and rs2291409), the endothelial cell nitric oxide synthase 3 (eNOS3) (rs1007311 and rs1799983) and the (VEGFA) (rs79469752, rs13207351, rs28357093, rs1570360 and rs3025039). These SNP alleles alter the TFBS for TF binding. Pair-wise LD was computed between SNPs. An increase in LD occurred in 32 pair-wise comparisons while a decrease was found in 22 pair-wise comparisons between the AMS and controls. Increases and decreases in LD pairs were found within and between signaling pathways and systems indicating the interaction of SNP alleles or potential TFBS from different areas of the genome. The most drastic change in TFBS occurs with ACE (I/D) SNP (rs4340) where the ACE-I allele generates 84 potential TFBS while the ACE-D allele generates only four binding sites. The alteration in TFBS generated by the 17 SNPs is discussed with respect to AMS.

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“…The people from the control group had lived at the 3600 M altitude for at least six months prior to being sampled. These sampling procedures have been previously described [8][9][10]31].…”

Section: Samplingmentioning

confidence: 99%

Section: Genotypingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

SNPs, Linkage Disequilibrium and Transcriptional Factor Binding Sites Associated with Acute Mountain Sickness among Han Chinese at the Qinghai-Tibetan Plateau

Buroker¹,

Xue²

2015

J Clin Med Genomics

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Sex‐biased gene regulation varies across human populations as a result of adaptive evolution

Reynolds,

Niedbalski

2023

American Journal of Biological Anthropology

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ObjectivesStudies of human sexual dimorphism and gender disparities in health focus on ostensibly universal molecular sex differences, such as sex chromosomes and circulating hormone levels, while ignoring the extraordinary diversity in biology, behavior, and culture acquired by different human populations over their unique evolutionary histories.Materials and MethodsUsing RNA‐Seq data and whole genome sequences from 1000G and HGDP, we investigate variation in sex‐biased gene expression across 11 human populations and test whether population‐level variation in sex‐biased expression may have resulted from adaptive evolution in regions containing sex‐specific regulatory variants.ResultsWe find that sex‐biased gene expression in humans is highly variable, mostly population‐specific, and demonstrates between population reversals. Expression quantitative trait locus mapping reveals sex‐specific regulatory regions with evidence of recent positive natural selection, suggesting that variation in sex‐biased expression may have evolved as an adaptive response to ancestral environments experienced by human populations.DiscussionThese results indicate that sex‐biased gene expression is more flexible than previously thought and is not generally shared among human populations. Instead, molecular phenotypes associated with sex depend on complex interactions between population‐specific molecular evolution and physiological responses to contemporary socioecologies.

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Neural network correlates of high‐altitude adaptive genetic variants in Tibetans: A pilot, exploratory study

Guo

Fan

et al. 2020

Human Brain Mapping

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Although substantial progress has been made in the identification of genetic substrates underlying physiology, neuropsychology, and brain organization, the genotype-phenotype associations remain largely unknown in the context of highaltitude (HA) adaptation. Here, we related HA adaptive genetic variants in three gene loci (EGLN1, EPAS1, and PPARA) to interindividual variance in a set of physiological characteristics, neuropsychological tests, and topological attributes of largescale structural and functional brain networks in 135 indigenous Tibetan highlanders. Analyses of individual HA adaptive single-nucleotide polymorphisms (SNPs) revealed that specific SNPs selectively modulated physiological characteristics (erythrocyte level, ratio between forced expiratory volume in the first second to forced vital capacity, arterial oxygen saturation, and heart rate) and structural network centrality (the left anterior orbital gyrus) with no effects on neuropsychology or functional brain networks. Further analyses of genetic adaptive scores, which summarized the overall degree of genetic adaptation to HA, revealed significant correlations only with structural brain networks with respect to local interconnectivity of the whole networks, intermodule communication between the right frontal and parietal module and the left occipital module, nodal centrality in several frontal regions, and connectivity strength of a subnetwork predominantly involving in intramodule edges in the right temporal and occipital module. Moreover, the associations were dependent on gene loci, weight types, or topological scales.Together, these findings shed new light on genotype-phenotype interactions under HA hypoxia and have important implications for developing new strategies to optimize organism and tissue responses to chronic hypoxia induced by extreme environments or diseases.

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EPAS1 and EGLN1 associations with high altitude sickness in Han and Tibetan Chinese at the Qinghai–Tibetan Plateau

Cited by 58 publications

References 36 publications

SNPs, Linkage Disequilibrium and Transcriptional Factor Binding Sites Associated with Acute Mountain Sickness among Han Chinese at the Qinghai-Tibetan Plateau

SNPs, Linkage Disequilibrium and Transcriptional Factor Binding Sites Associated with Acute Mountain Sickness among Han Chinese at the Qinghai-Tibetan Plateau

Sex‐biased gene regulation varies across human populations as a result of adaptive evolution

Neural network correlates of high‐altitude adaptive genetic variants in Tibetans: A pilot, exploratory study

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