Research Article

Clinical Autonomic Research

, Volume 19, Issue 6, pp 335-342

A role for succinate dehydrogenase genes in low chemoresponsiveness to hypoxia?

  • Jean-Paul RichaletAffiliated withUniversité Paris 13, UFR SMBH EA2363AP-HP, Hôpital Avicenne, Service de Physiologie, Explorations Fonctionnelles et Médecine du Sport Email author 
  • , Anne-Paule Gimenez-RoqueploAffiliated withAP-HP, Hôpital Européen Georges Pompidou, Département de GénétiqueINSERMCollège de FranceUniversité Paris Descartes
  • , Séverine PeyrardAffiliated withAP-HP, Hôpital Européen Georges Pompidou, Centre d’Investigations Cliniques 9201INSERM, Centre d’Investigations Cliniques 9201Université Paris Descartes
  • , Annabelle VénisseAffiliated withAP-HP, Hôpital Européen Georges Pompidou, Département de GénétiqueINSERMCollège de FranceUniversité Paris Descartes
  • , Laure MarelleAffiliated withAP-HP, Hôpital Européen Georges Pompidou, Centre d’Investigations Cliniques 9201
  • , Nelly BurnichonAffiliated withAP-HP, Hôpital Européen Georges Pompidou, Département de GénétiqueINSERMCollège de FranceAP-HP, Hôpital Européen Georges Pompidou, Centre d’Investigations Cliniques 9201
  • , Anissa BouzamondoAffiliated withUniversité Paris 13, UFR SMBH EA2363Société Française de Cardiologie
  • , Xavier JeunemaitreAffiliated withAP-HP, Hôpital Européen Georges Pompidou, Département de GénétiqueINSERMCollège de FranceUniversité Paris Descartes
  • , Michel AziziAffiliated withAP-HP, Hôpital Européen Georges Pompidou, Centre d’Investigations Cliniques 9201INSERM, Centre d’Investigations Cliniques 9201Université Paris Descartes
    • , Jean-Luc ElghoziAffiliated withAP-HP, Hôpital Necker, UF de Pharmacologie CliniqueUniversité Paris Descartes

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Abstract

The detection of hypoxia by the carotid bodies elicits a ventilatory response of utmost importance for tolerance to high altitude. Germline mutations in three genes encoding subunit B, C and D of succinate dehydrogenase (SDHB, SDHC and SDHD) have been associated with paragangliomas of the carotid body. We hypothesized that SDH dysfunction within the carotid body could result in low chemoresponsiveness and intolerance to high altitude. The frequency of polymorphisms of SDHs, hypoxia-inducible factor type 1 (HIF1α) and angiotensin converting enzyme (ACE) genes was compared between 40 subjects with intolerance to high altitude and a low hypoxic ventilatory response at exercise (HVRe ≤ 0.5 ml min−1 kg−1; HVR− group) and 41 subjects without intolerance to high altitude and a high HVRe (≥0.80 ml min−1 kg−1; HVR+). We found no significant association between low or high HVRe and (1) the allele frequencies for nine single nucleotide polymorphisms (SNPs) in the SDHD and SDHB genes, (2) the ACE insertion/deletion polymorphism and (3) four SNPs in the HIF1α gene. However, a marginal significant association was found between the synonymous polymorphism c.18A>C of the SDHB gene and chemoresponsiveness: 8/40 (20%) in the HVR− group and 3/41 (7%) in the HVR+ group (p = 0.12). A principal component analysis showed that no subject carrying the 18C allele had both high ventilatory and cardiac response to hypoxia. In conclusion, no clear association was found between gene variants involved in oxygen sensing and chemoresponsiveness, although some mutations in the SDHB and SDHD genes deserve further investigations in a larger population.

Keywords

Altitude tolerance Hypoxia Carotid bodies Ventilation