scholarly journals Effect of EGLN1 Genetic Polymorphisms on Hemoglobin Concentration in Andean Highlanders

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Yoshiki Yasukochi ◽  
Takayuki Nishimura ◽  
Juan Ugarte ◽  
Mayumi Ohnishi ◽  
Mika Nishihara ◽  
...  
Keyword(s):  
Hypoxia Inducible Factor ◽  
Hemoglobin Concentration ◽  
Genomic Region ◽  
Physiological Characteristic ◽  
Human Populations ◽  
Nucleotide Polymorphisms ◽  
Genetic Determinants ◽  
Hypoxia Inducible Factor 1 ◽  
Hb Concentration ◽  
The Relationship

The physiological characteristics of Andean natives living at high altitudes have been investigated extensively, with many studies reporting that Andean highlanders have a higher hemoglobin (Hb) concentration than other highlander populations. It has previously been reported that positive natural selection has acted independently on the egl-9 family hypoxia inducible factor 1 (EGLN1) gene in Tibetan and Andean highlanders and is related to Hb concentration in Tibetans. However, no study has yet revealed the genetic determinants of Hb concentration in Andeans even though several single-nucleotide polymorphisms (SNPs) in EGLN1 have previously been examined. Therefore, we explored the relationship between hematological measurements and tag SNPs designed to cover the whole EGLN1 genomic region in Andean highlanders living in Bolivia. Our findings indicated that haplotype frequencies estimated from the EGLN1 SNPs were significantly correlated with Hb concentration in the Bolivian highlanders. Moreover, we found that an Andean-dominant haplotype related to high Hb level may have expanded rapidly in ancestral Andean highlander populations. Analysis of genotype data in an ~436.3 kb genomic region containing EGLN1 using public databases indicated that the population structure based on EGLN1 genetic markers in Andean highlanders was largely different from that in other human populations. This finding may be related to an intrinsic or adaptive physiological characteristic of Andean highlanders. In conclusion, the high Hb concentrations in Andean highlanders can be partly characterized by EGLN1 genetic variants.

scholarly journals Germline polymorphisms in the Von Hippel-Lindau and Hypoxia-inducible factor 1-alpha genes, gene-environment and gene-gene interactions and renal cell cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jeroen A. A. van de Pol ◽  
Piet A. van den Brandt ◽  
Manon van Engeland ◽  
Roger W. L. Godschalk ◽  
Frederik-Jan van Schooten ◽  
...  
Keyword(s):  
Promoter Methylation ◽  
Cell Cancer ◽  
Hypoxia Inducible Factor ◽  
Gene Interactions ◽  
Nucleotide Polymorphisms ◽  
Von Hippel Lindau ◽  
Hypoxia Inducible Factor 1 ◽  
Gene Environment ◽  
The Relationship ◽  
Diet And Lifestyle

AbstractWe investigated the relationship between germline single nucleotide polymorphisms (SNPs) in Von Hippel-Lindau (VHL) and Hypoxia-inducible factor 1-alpha (HIF1A), and their gene-environment and gene-gene interactions, and clear-cell RCC (ccRCC) risk. Furthermore, we assessed the relationship between VHL SNPs and VHL promoter methylation. Three VHL polymorphisms and one HIF1A polymorphism were genotyped in the Netherlands Cohort Study. In 1986, 120,852 participants aged 55–69 completed a self-administered questionnaire on diet and lifestyle and toenail clippings were collected. Toenail DNA was genotyped using the Sequenom MassARRAY platform. After 20.3 years, 3004 subcohort members and 406 RCC cases, of which 263 ccRCC cases, were eligible for multivariate case-cohort analyses. VHL_rs779805 was associated with RCC (Hazard Ratio (HR) 1.53; 95% Confidence Interval (CI) 1.07–2.17) and ccRCC risk (HR 1.88; 95% CI 1.25–2.81). No associations were found for other SNPs. Potential gene-environment interactions were found between alcohol consumption and selected SNPs. However, none remained statistically significant after multiple comparison correction. No gene-gene interactions were observed between VHL and HIF1A. VHL promoter methylation was not associated with VHL SNPs. VHL SNPs may increase (cc)RCC susceptibility. No associations were found between gene-environment and gene-gene interactions and (cc)RCC risk and between VHL promoter methylation and VHL SNPs.

scholarly journals Multi-Omic Meta-Analysis of Transcriptomes and the Bibliome Uncovers Novel Hypoxia-Inducible Genes

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 582
Author(s):  
Yoko Ono ◽  
Hidemasa Bono
Keyword(s):  
Meta Analysis ◽  
Hypoxia Inducible Factor ◽  
Data Driven ◽  
Similarity Coefficients ◽  
Hypoxia Inducible Factor 1 ◽  
Response System ◽  
Inducible Genes ◽  
The Relationship ◽  
G Protein Coupled ◽  
Sufficient Oxygen

Hypoxia is a condition in which cells, tissues, or organisms are deprived of sufficient oxygen supply. Aerobic organisms have a hypoxic response system, represented by hypoxia-inducible factor 1-α (HIF1A), to adapt to this condition. Due to publication bias, there has been little focus on genes other than well-known signature hypoxia-inducible genes. Therefore, in this study, we performed a meta-analysis to identify novel hypoxia-inducible genes. We searched publicly available transcriptome databases to obtain hypoxia-related experimental data, retrieved the metadata, and manually curated it. We selected the genes that are differentially expressed by hypoxic stimulation, and evaluated their relevance in hypoxia by performing enrichment analyses. Next, we performed a bibliometric analysis using gene2pubmed data to examine genes that have not been well studied in relation to hypoxia. Gene2pubmed data provides information about the relationship between genes and publications. We calculated and evaluated the number of reports and similarity coefficients of each gene to HIF1A, which is a representative gene in hypoxia studies. In this data-driven study, we report that several genes that were not known to be associated with hypoxia, including the G protein-coupled receptor 146 gene, are upregulated by hypoxic stimulation.

scholarly journals Hypoxia-inducible factor–1 and associated upstream and downstream proteins in the pathophysiology and management of glioblastoma

2014 ◽  
Vol 37 (6) ◽  
pp. E8 ◽  
Author(s):  
Matthew Womeldorff ◽  
David Gillespie ◽  
Randy L. Jensen
Keyword(s):  
Cellular Response ◽  
Treatment Options ◽  
Hypoxia Inducible Factor ◽  
Hypoxia Inducible Factor 1 ◽  
Poor Patient ◽  
Growth Development ◽  
The Relationship ◽  
Insight Into ◽  
Upstream Regulators

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with an exceptionally poor patient outcome despite aggressive therapy including surgery, radiation, and chemotherapy. This aggressive phenotype may be associated with intratumoral hypoxia, which probably plays a key role in GBM tumor growth, development, and angiogenesis. A key regulator of cellular response to hypoxia is the protein hypoxia-inducible factor–1 (HIF-1). An examination of upstream hypoxic and nonhypoxic regulation of HIF-1 as well as a review of the downstream HIF-1–regulated proteins may provide further insight into the role of this transcription factor in GBM pathophysiology. Recent insights into upstream regulators that intimately interact with HIF-1 could provide potential therapeutic targets for treatment of this tumor. The same is potentially true for HIF-1–mediated pathways of glycolysis-, angiogenesis-, and invasion-promoting proteins. Thus, an understanding of the relationship between HIF-1, its upstream protein regulators, and its downstream transcribed genes in GBM pathogenesis could provide future treatment options for the care of patients with these tumors.

scholarly journals High altitude adaptation mitigates anemia risk associated with diabetes among the Mosuo of Southwest China

2018 ◽  
Author(s):  
M Su ◽  
K Wander ◽  
MK Shenk ◽  
T Blumenfield ◽  
H Li ◽  
...  
Keyword(s):  
Tibetan Plateau ◽  
High Altitude ◽  
Market Integration ◽  
Hypoxia Inducible Factor ◽  
Human Populations ◽  
The Tibetan Plateau ◽  
Low Oxygen ◽  
High Altitude Adaptation ◽  
Altitude Adaptation ◽  
Hb Concentration

AbstractHuman populations native to high altitude regions (≥2500 m) exhibit numerous adaptations to hypoxic stress. On the Tibetan Plateau, these include modifications of the hypoxia inducible factor (HIF) pathway to essentially uncouple erythropoiesis (red blood cell production) and blood hemoglobin (Hb) concentration—which normally increase in response to low oxygen—from hypoxia. Uncoupling of erythropoiesis and hypoxia is also observed among people with diabetes due to damage to kidney tissues. This is hypothesized to result in elevated risk for anemia among diabetics, which increases risk for cardiovascular disease and death. We tested the hypothesis that the independence of erythropoiesis from HIF among high-altitude adapted populations of the Tibetan Plateau may protect against diabetes-associated anemia. We investigated this hypothesis among the Mosuo, a population living in Yunnan Province, China (at ~2800 m altitude) that is undergoing rapid market integration and lifestyle change, with concomitant increase in risk for type 2 diabetes. We found that, although diabetes (glycated hemoglobin, HbA1c ≥6.5%) is associated with anemia (females: Hb<12g/dl; males: Hb<13g/dl) among the Chinese population as a whole (N: 5,606; OR: 1.48; p: 0.008), this is not the case among the Mosuo (N: 316; OR: 1.36; p: 0.532). Both pathways uncoupling hypoxia from erythropoiesis (diabetic disease and high altitude adaptation) are incompletely understood; their intersection in protecting Mosuo with diabetes from anemia may provide insight into the mechanisms underlying each. Further, these findings point to the importance of understanding how high-altitude adaptations interact with chronic disease processes, as populations like the Mosuo experience rapid market integration.

scholarly journals Substance P aggravates periodontitis by  upregulating HIF-1 α and RANKL / OPG ratio

2019 ◽  
Author(s):  
Kaixian Yan ◽  
Qin Lin ◽  
Kailiang Tang ◽  
Shuang Liu ◽  
Yi Du ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Substance P ◽  
Hypoxia Inducible Factor ◽  
Gingival Fibroblasts ◽  
Normal Tissues ◽  
Hypoxia Inducible Factor 1 ◽  
Receptor Activator ◽  
Porphyromonas Gingivalis Lipopolysaccharide ◽  
Trap Staining ◽  
The Relationship

Abstract Background Both substance P (SP) and hypoxia-inducible factor 1 alpha (HIF-1α) get involved in inflammation and angiogenesis. But the interrelation between SP and HIF-1α in rat periodontitis is still little known. Methods Ligation‐induced rat periodontitis was established to observe the expression of SP and HIF-1α by immunohistochemistry. Gingival fibroblasts and bone marrow macrophages (BMMs) were respectively cultured and stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). 10 nM SP with or without 1µg/ml LPS was added to elaborate the relationship between SP and HIF-1α in gingival fibroblasts. The effect of SP on osteoclastogenesis was tested by TRAP staining. Western blotting was applied to investigate the expressions of HIF-1α, osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL). Results The expression levels of HIF-1α and SP were higher in periodontitis than normal tissues. SP could upregulate the level of HIF-1α and RANKL/OPG ratio in LPS-stimulated gingival fibroblasts. SP with or without LPS also facilitated RANKL induced osteoclastogenesis. Conclusion Substance P aggravates periodontitis by increasing HIF-1α and RANKL / OPG ratio.

Effect of hemoglobin concentration on maximal O2 uptake in canine gastrocnemius muscle in situ

1991 ◽  
Vol 70 (3) ◽  
pp. 1105-1112 ◽  
Author(s):  
M. C. Hogan ◽  
D. E. Bebout ◽  
P. D. Wagner
Keyword(s):  
Gastrocnemius Muscle ◽  
Random Sequence ◽  
Hemoglobin Concentration ◽  
Random Order ◽  
O2 Uptake ◽  
Blood Flows ◽  
Hb Concentration ◽  
O2 Delivery ◽  
The Relationship

O2 delivery to maximally working muscle was decreased by altering hemoglobin (Hb) concentration and arterial PO2 (PaO2) to investigate whether the reductions in maximal O2 uptake (VO2max) that occur with lowered [Hb] are in part related to changes in the effective muscle O2 diffusing capacity (DmO2). Two sets of experiments were conducted. In the initial set (n = 8), three levels of Hb [5.8 +/- 0.3, 9.4 +/- 0.1, and 14.4 +/- 0.6 (SE) g/100 ml] in the blood were used in random order to pump perfuse, at equal muscle blood flows and PaO2, maximally working isolated dog gastrocnemius muscle. VO2max declined with decreasing [Hb], but the relationship between VO2max and both the effluent venous PO2 (PvO2) and the calculated mean capillary PO2 (PcO2) was not linear through the origin and, therefore, not compatible with a single value of DmO2 (as calculated by Bohr integration using a model based on Fick's law of diffusion). To clarify these results, a second set of experiments (n = 6) was conducted in which two levels of Hb (14.0 +/- 0.6 and 6.9 +/- 0.6 g/100 ml) were each combined with two levels of oxygenation (PaO2 79 +/- 8 and 29 +/- 2 Torr) and applied in random sequence to again pump perfuse maximally working dog gastrocnemius muscle at constant blood flow. In these experiments, the relationship between VO2max and both PvO2 and calculated PcO2 for each [Hb] was consistent with a constant estimate of DmO2 as PaO2 was reduced, but the calculated DmO2 for the lower [Hb] was 33% less than that at the higher [Hb] (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Genetic Variations in the Hypoxia-Inducible Factor-1αGene and Lung Cancer

2009 ◽  
Vol 234 (9) ◽  
pp. 1109-1116 ◽  
Author(s):  
Ece Konac ◽  
Irem Dogan ◽  
Hacer Ilke Onen ◽  
Ahmet Selim Yurdakul ◽  
Can Ozturk ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Hypoxia Inducible Factor ◽  
Tumor Hypoxia ◽  
Turkish Population ◽  
Lung Cancer Patients ◽  
Hypoxia Inducible Factor 1 ◽  
Significant Difference ◽  
Tumor Survival ◽  
The Relationship ◽  
Exon 10

Hypoxia-inducible factor-1 ( HIF-1), an important genetic component of angiogenesis, becomes stable as a response to tumor hypoxia and facilitates tumor survival. The polymorphisms of the HIF-1αgene may cause changes in the activity of this protein, which serves as a transcription factor for many genes in tumorigenesis. In this study, we have investigated the relationship between seven HIF-1αpolymorphisms [C > T substitution in intron 8 (rs10873142), T418I (rs41508050) in exon 10, P564P (rs41492849), L580L (rs34005929), P582S (rs11549465), A588T (rs11549467) in exon 12 and dinucleotide GT repeats in intron 13 (rs10645014)] among lung cancer patients in the Turkish population. Genomic DNA was isolated from 141 lung cancer cases and 156 controls and subjected to PCR for amplification. Genotyping was carried out with RFLP and DNA sequencing methods. There was no significant difference between the lung cancer cases and controls in terms of the distribution of genotyping frequencies of seven HIF-1αpolymorphisms ( P > 0.05). No significant relationship was found between the C > T substitution in intron 8 and P582S haplotypes and development of lung cancer. In addition, there were no significant associations between the genotypes and clinopathological characteristics of the cases examined. These findings show that polymorphisms in the HIF-1αgene do not confer susceptibility to lung cancer. Exp Biol Med 234:1109–1116, 2009

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