The HMOX2 polymorphism contributes to the carotid body chemoreflex in European sea-level residents by regulating hypoxic ventilatory responses
This study investigates whether a functional single nucleotide polymorphism of HMOX2 (heme oxygenase-2) (rs4786504 T>C) is involved in individual chemosensitivity to acute hypoxia, as assessed by ventilatory responses, in European individuals. These responses were obtained at rest and during...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmed.2022.1000786/full |
| _version_ | 1797990373656625152 |
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| author | Pierre Fabries Pierre Fabries Pierre Fabries Catherine Drogou Catherine Drogou Fabien Sauvet Fabien Sauvet Fabien Sauvet Olivier Nespoulous Marie-Claire Erkel Marie-Claire Erkel Vincent Marchandot Walid Bouaziz Benoît Lepetit Benoît Lepetit Anne-Pia Hamm-Hornez Alexandra Malgoyre Alexandra Malgoyre Nathalie Koulmann Nathalie Koulmann Danielle Gomez-Merino Danielle Gomez-Merino Mounir Chennaoui Mounir Chennaoui |
| author_facet | Pierre Fabries Pierre Fabries Pierre Fabries Catherine Drogou Catherine Drogou Fabien Sauvet Fabien Sauvet Fabien Sauvet Olivier Nespoulous Marie-Claire Erkel Marie-Claire Erkel Vincent Marchandot Walid Bouaziz Benoît Lepetit Benoît Lepetit Anne-Pia Hamm-Hornez Alexandra Malgoyre Alexandra Malgoyre Nathalie Koulmann Nathalie Koulmann Danielle Gomez-Merino Danielle Gomez-Merino Mounir Chennaoui Mounir Chennaoui |
| author_sort | Pierre Fabries |
| collection | DOAJ |
| description | This study investigates whether a functional single nucleotide polymorphism of HMOX2 (heme oxygenase-2) (rs4786504 T>C) is involved in individual chemosensitivity to acute hypoxia, as assessed by ventilatory responses, in European individuals. These responses were obtained at rest and during submaximal exercise, using a standardized and validated protocol for exposure to acute normobaric hypoxia. Carriers of the ancestral T allele (n = 44) have significantly lower resting and exercise hypoxic ventilatory responses than C/C homozygous carriers (n = 40). In the literature, a hypoxic ventilatory response threshold to exercise has been identified as an independent predictor of severe high altitude-illness (SHAI). Our study shows that carriers of the T allele have a higher risk of SHAI than carriers of the mutated C/C genotype. Secondarily, we were also interested in COMT (rs4680 G > A) polymorphism, which may be indirectly involved in the chemoreflex response through modulation of autonomic nervous system activity. Significant differences are present between COMT genotypes for oxygen saturation and ventilatory responses to hypoxia at rest. In conclusion, this study adds information on genetic factors involved in individual vulnerability to acute hypoxia and supports the critical role of the ≪ O2 sensor ≫ - heme oxygenase-2 - in the chemosensitivity of carotid bodies in Humans. |
| first_indexed | 2024-04-11T08:35:33Z |
| format | Article |
| id | doaj.art-5e328c69f01e4c1c97a1dc86cd6264ee |
| institution | Directory Open Access Journal |
| issn | 2296-858X |
| language | English |
| last_indexed | 2024-04-11T08:35:33Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Medicine |
| spelling | doaj.art-5e328c69f01e4c1c97a1dc86cd6264ee2022-12-22T04:34:20ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2022-11-01910.3389/fmed.2022.10007861000786The HMOX2 polymorphism contributes to the carotid body chemoreflex in European sea-level residents by regulating hypoxic ventilatory responsesPierre Fabries0Pierre Fabries1Pierre Fabries2Catherine Drogou3Catherine Drogou4Fabien Sauvet5Fabien Sauvet6Fabien Sauvet7Olivier Nespoulous8Marie-Claire Erkel9Marie-Claire Erkel10Vincent Marchandot11Walid Bouaziz12Benoît Lepetit13Benoît Lepetit14Anne-Pia Hamm-Hornez15Alexandra Malgoyre16Alexandra Malgoyre17Nathalie Koulmann18Nathalie Koulmann19Danielle Gomez-Merino20Danielle Gomez-Merino21Mounir Chennaoui22Mounir Chennaoui23French Armed Forces Biomedical Research Institute – IRBA, Brétigny-sur-Orge, FranceFrench Military Health Academy - Ecole du Val-de-Grâce, Paris, FranceLaboratoire de Biologie de l'Exercice pour la Performance et la Santé – LBEPS – UMR, Université Paris-Saclay, IRBA, Evry-Courcouronnes, FranceFrench Armed Forces Biomedical Research Institute – IRBA, Brétigny-sur-Orge, FranceVigilance Fatigue Sommeil et Santé Publique – VIFASOM – UPR 7330, Université de Paris Cité, Paris, FranceFrench Armed Forces Biomedical Research Institute – IRBA, Brétigny-sur-Orge, FranceFrench Military Health Academy - Ecole du Val-de-Grâce, Paris, FranceVigilance Fatigue Sommeil et Santé Publique – VIFASOM – UPR 7330, Université de Paris Cité, Paris, FranceFrench Armed Forces Biomedical Research Institute – IRBA, Brétigny-sur-Orge, FranceFrench Armed Forces Biomedical Research Institute – IRBA, Brétigny-sur-Orge, FranceVigilance Fatigue Sommeil et Santé Publique – VIFASOM – UPR 7330, Université de Paris Cité, Paris, France41ème Antenne médicale, 5ème Centre médical des Armées, Dieuze, FranceFrench Armed Forces Biomedical Research Institute – IRBA, Brétigny-sur-Orge, FranceFrench Armed Forces Biomedical Research Institute – IRBA, Brétigny-sur-Orge, FranceLaboratoire de Biologie de l'Exercice pour la Performance et la Santé – LBEPS – UMR, Université Paris-Saclay, IRBA, Evry-Courcouronnes, FranceAeromedical Center – CPEMPN – Percy Military Hospital, Clamart, FranceFrench Armed Forces Biomedical Research Institute – IRBA, Brétigny-sur-Orge, FranceLaboratoire de Biologie de l'Exercice pour la Performance et la Santé – LBEPS – UMR, Université Paris-Saclay, IRBA, Evry-Courcouronnes, FranceFrench Military Health Academy - Ecole du Val-de-Grâce, Paris, FranceLaboratoire de Biologie de l'Exercice pour la Performance et la Santé – LBEPS – UMR, Université Paris-Saclay, IRBA, Evry-Courcouronnes, FranceFrench Armed Forces Biomedical Research Institute – IRBA, Brétigny-sur-Orge, FranceVigilance Fatigue Sommeil et Santé Publique – VIFASOM – UPR 7330, Université de Paris Cité, Paris, FranceFrench Armed Forces Biomedical Research Institute – IRBA, Brétigny-sur-Orge, FranceVigilance Fatigue Sommeil et Santé Publique – VIFASOM – UPR 7330, Université de Paris Cité, Paris, FranceThis study investigates whether a functional single nucleotide polymorphism of HMOX2 (heme oxygenase-2) (rs4786504 T>C) is involved in individual chemosensitivity to acute hypoxia, as assessed by ventilatory responses, in European individuals. These responses were obtained at rest and during submaximal exercise, using a standardized and validated protocol for exposure to acute normobaric hypoxia. Carriers of the ancestral T allele (n = 44) have significantly lower resting and exercise hypoxic ventilatory responses than C/C homozygous carriers (n = 40). In the literature, a hypoxic ventilatory response threshold to exercise has been identified as an independent predictor of severe high altitude-illness (SHAI). Our study shows that carriers of the T allele have a higher risk of SHAI than carriers of the mutated C/C genotype. Secondarily, we were also interested in COMT (rs4680 G > A) polymorphism, which may be indirectly involved in the chemoreflex response through modulation of autonomic nervous system activity. Significant differences are present between COMT genotypes for oxygen saturation and ventilatory responses to hypoxia at rest. In conclusion, this study adds information on genetic factors involved in individual vulnerability to acute hypoxia and supports the critical role of the ≪ O2 sensor ≫ - heme oxygenase-2 - in the chemosensitivity of carotid bodies in Humans.https://www.frontiersin.org/articles/10.3389/fmed.2022.1000786/fullacute hypoxiaexercisechemosensitivityheme oxygenase-2geneticsindividual vulnerability |
| spellingShingle | Pierre Fabries Pierre Fabries Pierre Fabries Catherine Drogou Catherine Drogou Fabien Sauvet Fabien Sauvet Fabien Sauvet Olivier Nespoulous Marie-Claire Erkel Marie-Claire Erkel Vincent Marchandot Walid Bouaziz Benoît Lepetit Benoît Lepetit Anne-Pia Hamm-Hornez Alexandra Malgoyre Alexandra Malgoyre Nathalie Koulmann Nathalie Koulmann Danielle Gomez-Merino Danielle Gomez-Merino Mounir Chennaoui Mounir Chennaoui The HMOX2 polymorphism contributes to the carotid body chemoreflex in European sea-level residents by regulating hypoxic ventilatory responses Frontiers in Medicine acute hypoxia exercise chemosensitivity heme oxygenase-2 genetics individual vulnerability |
| title | The HMOX2 polymorphism contributes to the carotid body chemoreflex in European sea-level residents by regulating hypoxic ventilatory responses |
| title_full | The HMOX2 polymorphism contributes to the carotid body chemoreflex in European sea-level residents by regulating hypoxic ventilatory responses |
| title_fullStr | The HMOX2 polymorphism contributes to the carotid body chemoreflex in European sea-level residents by regulating hypoxic ventilatory responses |
| title_full_unstemmed | The HMOX2 polymorphism contributes to the carotid body chemoreflex in European sea-level residents by regulating hypoxic ventilatory responses |
| title_short | The HMOX2 polymorphism contributes to the carotid body chemoreflex in European sea-level residents by regulating hypoxic ventilatory responses |
| title_sort | hmox2 polymorphism contributes to the carotid body chemoreflex in european sea level residents by regulating hypoxic ventilatory responses |
| topic | acute hypoxia exercise chemosensitivity heme oxygenase-2 genetics individual vulnerability |
| url | https://www.frontiersin.org/articles/10.3389/fmed.2022.1000786/full |
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