RESEARCH ARTICLE A role for succinate dehydrogenase genes in low chemoresponsiveness to hypoxia? Jean-Paul Richalet ® Anne-Paule Gimenez-Roqueplo ® Se ´verine Peyrard ® Annabelle Ve ´nisse ® Laure Marelle ® Nelly Burnichon ® Anissa Bouzamondo ® Xavier Jeunemaitre ® Michel Azizi ® Jean-Luc Elghozi Received: 1 April 2009 / Accepted: 12 August 2009 / Published online: 19 September 2009 Ó Springer-Verlag 2009 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 dehy- drogenase (SDHB, SDHC and SDHD) have been associ- ated with paragangliomas of the carotid body. We hypothesized that SDH dysfunction within the carotid body could result in low chemoresponsiveness and intol- erance to high altitude. The frequency of polymorphisms of SDHs, hypoxia-inducible factor type 1 (HIF1a) and angiotensin converting enzyme (ACE) genes was com- pared between 40 subjects with intolerance to high alti- tude and a low hypoxic ventilatory response at exercise (HVRe B 0.5 ml min -1 kg -1 ; HVR- group) and 41 subjects without intolerance to high altitude and a high HVRe (C0.80 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 poly- morphisms (SNPs) in the SDHD and SDHB genes, (2) the ACE insertion/deletion polymorphism and (3) four SNPs in the HIF1a gene. However, a marginal significant association was found between the synonymous poly- morphism c.18A [ C of the SDHB gene and chemore- sponsiveness: 8/40 (20%) in the HVR- group and 3/41 (7%) in the HVR? group (p = 0.12). A principal com- ponent 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. J.-P. Richalet (&) Universite ´ Paris 13, UFR SMBH EA2363, 74 Rue Marcel Cachin, 93017 Bobigny Cedex, France e-mail: richalet@smbh.univ-paris13.fr J.-P. Richalet AP-HP, Ho ˆpital Avicenne, Service de Physiologie, Explorations Fonctionnelles et Me ´decine du Sport, Bobigny, France J.-L. Elghozi AP-HP, Ho ˆpital Necker, UF de Pharmacologie Clinique, 75015 Paris, France A.-P. Gimenez-Roqueplo Á A. Ve ´nisse Á N. Burnichon Á X. Jeunemaitre AP-HP, Ho ˆpital Europe ´en Georges Pompidou, De ´partement de Ge ´ne ´tique, Paris, France A.-P. Gimenez-Roqueplo Á A. Ve ´nisse Á N. Burnichon Á X. Jeunemaitre INSERM, Unite ´ 970, Paris, France A.-P. Gimenez-Roqueplo Á A. Ve ´nisse Á N. Burnichon Á X. Jeunemaitre Colle `ge de France, Paris, France S. Peyrard Á L. Marelle Á N. Burnichon Á M. Azizi AP-HP, Ho ˆpital Europe ´en Georges Pompidou, Centre d’Investigations Cliniques 9201, Paris, France S. Peyrard Á M. Azizi INSERM, Centre d’Investigations Cliniques 9201, Paris, France A.-P. Gimenez-Roqueplo Á S. Peyrard Á A. Ve ´nisse Á X. Jeunemaitre Á M. Azizi Á J.-L. Elghozi Universite ´ Paris Descartes, Paris, France A. Bouzamondo Socie ´te ´ Franc ¸aise de Cardiologie, Paris, France 123 Clin Auton Res (2009) 19:335–342 DOI 10.1007/s10286-009-0028-z