Gene-Gene Interaction between EPAS1 and EGLN1 in Patients with High-Altitude Pulmonary Edema

Horiuchi, Toshimichi; Droma, Yunden; Kinota, Fumiya; Kobayashi, Nozomu; Ôta, Masao; Hanaoka, Masayuki

doi:10.1183/13993003.congress-2018.pa3060

Cited by 2 publications

(3 citation statements)

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“…16 . The seven polymorphisms of EGLN1 gene-rs1538664, rs479200, rs2486729, rs2790879, rs480902, rs2486736 and rs973252; were found to be significantly different in HAPE patients and HAPE controls 14 . A significant number of patients in severe COVID-19 mimic HAPE hypoxia 17 .…”

Section: Introductionmentioning

confidence: 85%

“…Among the several genotypes of the EGLN1 gene, six of them (rs2472261, rs480902, rs479200, rs2808611, rs2153364, rs2491405) are present in the various ethnic populations of India 13 . Specifically, rs479200 and rs480902 SNPs have been repeatedly implicated for significant associations with HAPE patients 5,14 . Mishra et al 15 have observed a multi-fold increase in EGLN1 expression in HAPE patients and significant association with the risk genotypes, their haplotypes and interacting genotypes.…”

Section: Introductionmentioning

confidence: 99%

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C allele of rs479200 of the host EGLN1 gene - a risk factor for severe COVID-19 (pilot study)

Harit

Singh

et al. 2022

Preprint

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Background Coronavirus disease-2019 (COVID-19) symptoms can range from asymptomatic, moderate to severe manifestations that result in an overall global case fatality rate of 2-7 %. While each variant has had it challenges, and some variants are more severe than others, risk factors of severe COVID-19 are still under investigation. In this context, the host genetic predisposition is also a crucial factor to investigate. In the present study, we investigated host genotypes of the SNP rs479200 of the host EGLN1 gene, previously implicated in high altitude pulmonary edema (HAPE), some of whose symptoms such as hypoxia profoundly overlap with severe COVID-19. Methods After informed consent, 158 RT-PCR confirmed COVID-19 patients (March 2020 to June 2021) were enrolled in the study. Based on their clinical manifestations, disease severity was categorized by the clinical team. Blood samples were drawn and DNA was extracted from the clot to infer different genotypes of the SNP rs479200 of the host EGLN1 gene. PCR-RFLP analysis of the SNP rs479200 (C > T) was performed with an amplicon size of 367 bp. Various genotypes (TT, TC and CC) were assigned based on the presence/absence of a restriction site (T/GTACA) for restriction enzyme BsrGI. Allele frequencies, Hardy-Weinberg Equilibrium (HWE) and multinomial logistic regression were performed using statistical tool SPSS version 23 (IBM). Findings We observed that the severe COVID-19 category was composed of comparatively younger patients with mean age (34.9), compared to asymptomatic and moderate categories whose mean age was 49.7 and 54.3, respectively. Preponderance of males and high heterozygosity (TC) was observed across the clinical categories. Notably, the frequency of C allele (0.664) was 2-fold higher than the T allele (0.336) in severe COVID-19 patients, whereas the allele frequencies were similar in asymptomatic and moderate category of COVID-19 patients. Multinomial logistic regression showed an association of genotypes with increasing clinical severity; odds ratio (adjusted OR- 11.414 (2.564-50.812)) and (unadjusted OR- 6.214 (1.84-20.99)) for the genotype CC in severe category of COVID-19. Interestingly, the TC genotype was also found to be positively associated with severe outcome (unadjusted OR-5.816 (1.489-22.709)), indicating association of C allele in imparting the risk of severe outcome. Interpretation The study provides strong evidence that the presence of C allele of SNP (rs479200) of the EGLN1 gene associates with severity in COVID-19 patients. Thus, the presence of C allele may be a risk factor for COVID-19 severity. This study opens new avenues towards risk assessment that include EGLN1 (rs479200) genotype testing and identifying patients with C allele who might be prioritized for critical care.

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Section: Introductionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

C allele of rs479200 of the host EGLN1 gene - a risk factor for severe COVID-19 (pilot study)

Harit

Singh

et al. 2022

Preprint

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“…However, the putative adaptive alleles in highlander populations appeared to be maladaptive to the acute hypobaric hypoxic exposure in the Japanese cohort, likely due to the difference of genetic backgrounds between the ethnic groups [36]. In addition, the interaction of EGLN1 SNPs and the endothelial PAS domain protein 1 (EPAS1) gene may affect the prevalence of HAPE in Japanese individuals [37]. Consequently, EGLN1 is likely involved in the regulation of the cardiovascular system and in the adaptation to high-altitudes.…”

Section: Introductionmentioning

confidence: 94%

Effect of EGLN1 Genetic Polymorphisms on Hemoglobin Concentration in Andean Highlanders

Yasukochi

Nishimura

Ugarte

et al. 2020

BioMed Research International

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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.

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Gene-Gene Interaction between EPAS1 and EGLN1 in Patients with High-Altitude Pulmonary Edema

Cited by 2 publications

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C allele of rs479200 of the host EGLN1 gene - a risk factor for severe COVID-19 (pilot study)

C allele of rs479200 of the host EGLN1 gene - a risk factor for severe COVID-19 (pilot study)

Effect of EGLN1 Genetic Polymorphisms on Hemoglobin Concentration in Andean Highlanders

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