Dataset Information

Association of EGLN1 genetic polymorphisms with SpO₂ responses to acute hypobaric hypoxia in a Japanese cohort.

ABSTRACT:

Background

Recent studies have explored various genetic and physiological factors related to high-altitude adaptation in highlander populations. However, the effects of single nucleotide polymorphisms (SNPs), influencing such adaptation, on physiological responses to hypobaric hypoxia have not been examined in lowlanders with lowlander ancestry. Thus, we aimed to investigate the association between SNPs around the EGLN1 genomic region, possibly involved in high-altitude adaptation, and physiological changes to hypobaric hypoxia exposure in a cohort of Japanese lowlanders.

Methods

Physiological data were obtained from 46 healthy Japanese male students under different atmospheric pressure conditions (equivalent to sea level and altitudes of 2500 and 4000 m). Genotypes of seven SNPs around EGLN1 were determined in all subjects by PCR-direct sequencing or TaqMan SNP genotyping assay.

Results

Results of the association study suggest that percutaneous arterial oxygen saturation (SpO₂) responses of individuals with rs12097901 and rs2790859 alleles, whose frequencies are high in highlander populations (HL alleles), may be susceptible to acute hypobaric hypoxia. SpO₂ levels of individuals with HL alleles were lower than those of individuals with non-HL alleles. At the same time, the subjects with HL alleles did not appear to have any remarkable hematological or pulmonary features that may counteract the low levels of SpO₂. One may hypothesize that the low SpO₂ levels in HL allele carriers could be a risk factor for acute mountain sickness in Japanese population.

Conclusions

Our findings suggest that rs12097901 and rs2790859 genotypes affect SpO₂ responses and may be associated with the susceptibility to acute hypobaric hypoxia in Japanese population.

SUBMITTER: Yasukochi Y

PROVIDER: S-EPMC5889538 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Both hypoxia and inhibition of 2-oxoglutarate dehydrogenase complex (OGDHC) are known to change cellular amino acid pools, but the quantitative comparison of the metabolic and physiological outcomes has not been done. We hypothesize that OGDHC inhibition models metabolic changes caused by hypoxia, as both perturb the respiratory chain function, limiting either the NADH (OGDHC inhibition) or oxygen (hypoxia) supply. In the current study, we quantify the changes in the amino acid metabolism after OGDHC inhibition in the highly sensitive to hypoxia cerebellum and compare them to the earlier characterized changes after acute hypobaric hypoxia. In addition, the associated physiological effects are characterized and compared. A specific OGDHC inhibitor succinyl phosphonate (SP) is shown to act similar to hypoxia, increasing levels of many amino acids in the cerebellum of non-pregnant rats, without affecting those in the pregnant rats. Compared with hypoxia, stronger effects of SP in non-pregnant rats are observed on the levels of cerebellar amino acids, electrocardiography (ECG), and freezing time. In pregnant rats, hypoxia affects ECG and behavior more than SP, although none of the stressors significantly change the levels of cerebellar amino acids. The biochemical differences underlying the different physiological actions of SP and hypoxia are revealed by correlation analysis of the studied parameters. The negative correlations of cerebellar amino acids with OGDHC and/or tryptophan, shown to arise after the action of SP and hypoxia, discriminate the overall metabolic action of the stressors. More negative correlations are induced in the non-pregnant rats by hypoxia, and in the pregnant rats by SP. Thus, our findings indicate that the OGDHC inhibition mimics the action of acute hypobaric hypoxia on the cerebellar amino acid levels, but a better prediction of the physiological outcomes requires assessment of integral network changes, such as increases in the negative correlations among the amino acids, OGDHC, and/or tryptophan.

Dataset Information

Association of EGLN1 genetic polymorphisms with SpO₂ responses to acute hypobaric hypoxia in a Japanese cohort.

Background

Methods

Results

Conclusions

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OmicsDI is part of the ELIXIR infrastructure

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Association of EGLN1 genetic polymorphisms with SpO2 responses to acute hypobaric hypoxia in a Japanese cohort.

Background

Methods

Results

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OmicsDI is part of the ELIXIR infrastructure

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Association of EGLN1 genetic polymorphisms with SpO₂ responses to acute hypobaric hypoxia in a Japanese cohort.