Clinical Autonomic Research

, 19:335

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

  • Jean-Paul Richalet
  • Anne-Paule Gimenez-Roqueplo
  • Séverine Peyrard
  • Annabelle Vénisse
  • Laure Marelle
  • Nelly Burnichon
  • Anissa Bouzamondo
  • Xavier Jeunemaitre
  • Michel Azizi
  • Jean-Luc Elghozi
Research Article

DOI: 10.1007/s10286-009-0028-z

Cite this article as:
Richalet, J., Gimenez-Roqueplo, A., Peyrard, S. et al. Clin Auton Res (2009) 19: 335. doi:10.1007/s10286-009-0028-z

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 toleranceHypoxiaCarotid bodiesVentilation

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Jean-Paul Richalet
    • 1
    • 2
  • Anne-Paule Gimenez-Roqueplo
    • 4
    • 5
    • 6
    • 9
  • Séverine Peyrard
    • 7
    • 8
    • 9
  • Annabelle Vénisse
    • 4
    • 5
    • 6
    • 9
  • Laure Marelle
    • 7
  • Nelly Burnichon
    • 4
    • 5
    • 6
    • 7
  • Anissa Bouzamondo
    • 10
  • Xavier Jeunemaitre
    • 4
    • 5
    • 6
    • 9
  • Michel Azizi
    • 7
    • 8
    • 9
  • Jean-Luc Elghozi
    • 3
    • 9
  1. 1.Université Paris 13, UFR SMBH EA2363Bobigny CedexFrance
  2. 2.AP-HP, Hôpital Avicenne, Service de Physiologie, Explorations Fonctionnelles et Médecine du SportBobignyFrance
  3. 3.AP-HP, Hôpital Necker, UF de Pharmacologie CliniqueParisFrance
  4. 4.AP-HP, Hôpital Européen Georges Pompidou, Département de GénétiqueParisFrance
  5. 5.INSERMParisFrance
  6. 6.Collège de FranceParisFrance
  7. 7.AP-HP, Hôpital Européen Georges Pompidou, Centre d’Investigations Cliniques 9201ParisFrance
  8. 8.INSERM, Centre d’Investigations Cliniques 9201ParisFrance
  9. 9.Université Paris DescartesParisFrance
  10. 10.Société Française de CardiologieParisFrance