Relationship Between Succinate Dehydrogenase Mutations and High-Altitude Illness

Relationship Between Succinate Dehydrogenase Mutations and High-Altitude Illness Associated With Chemoreflex Failure

This study is is the first step of a full study named CHEMOGENE because it explores the genetic determinant of an alteration of the chemoreflex. This reflex determines hyperventilation when the pressure of oxygen falls in the blood. This happens when subjects travel to high-altitude where oxygen levels diminish in the atmosphere. Subjects with such an altered chemoreflex are intolerant to altitude and develop pulmonary or cerebral edema associated with a severe headache. In this study we compare subjects tolerant to high altitude (8000 meters)to subjects intolerant to altitude. The chemoreflex is measured i.e. the hyperventilation associated with hypoxia and all subjects are scanned for the genes implicated in the mitochondrial respiratory chain. The idea is that subjects with an impaired oxygen sensing will exhibit an altered chemoreflex and will be intolerant to high-altitude.

Study Overview

• Status: Completed
• Conditions: Altitude Intolerance; High-Altitude Illness

Detailed Description

Subjects are selected at an outpatient clinic specialised in the diagnosis of tolerance to altitude, where the chemoreflex is analyzed during a bicycle exercise performed with a oxygen deprived air simulating a 8000 meters altitude.

All subjects will go later to high altitude for trekking usually. The patients are those subjects with an altered chemoreflex who exhibited cerebral edema or pulmonary edema during the trekking.

The controls are the subjects with a normal chemoreflex who did not exhibit any trouble during their journey.

Fourty subjects of each group are included. A blood sample is withdrawn and studied for succinate dehydrogenase genes in a blind fashion.

After completing the inclusion the allelic mutations will be compared in the two groups.

• Study Type: Observational
• Enrollment (Actual): 83

Contacts and Locations

Study Locations

• France
  • Paris, France, 75908
    • Centre d'Investigation Clinique, Hopital Pompidou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chemoreflex sensitivity measured (normal or pathologic)
• Journey to high-altitude (well tolerated or with a severe disease such as pulmonary edema or cerebral edema)

Exclusion Criteria:

• Asthma,
• Arterial hypertension,
• Drug treatment

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: Société Française de Cardiologie
• Investigators: Principal Investigator: Jean-Luc ELGHOZI, Prof., Institut National de la Sante et de la Recherche Medicale U 652

Publications and helpful links

General Publications

• Gimenez-Roqueplo AP, Favier J, Rustin P, Rieubland C, Crespin M, Nau V, Khau Van Kien P, Corvol P, Plouin PF, Jeunemaitre X; COMETE Network. Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas. Cancer Res. 2003 Sep 1;63(17):5615-21.
• Gimenez-Roqueplo AP, Favier J, Rustin P, Rieubland C, Kerlan V, Plouin PF, Rotig A, Jeunemaitre X. Functional consequences of a SDHB gene mutation in an apparently sporadic pheochromocytoma. J Clin Endocrinol Metab. 2002 Oct;87(10):4771-4. doi: 10.1210/jc.2002-020525.
• Gimenez-Roqueplo AP, Favier J, Rustin P, Mourad JJ, Plouin PF, Corvol P, Rotig A, Jeunemaitre X. The R22X mutation of the SDHD gene in hereditary paraganglioma abolishes the enzymatic activity of complex II in the mitochondrial respiratory chain and activates the hypoxia pathway. Am J Hum Genet. 2001 Dec;69(6):1186-97. doi: 10.1086/324413. Epub 2001 Oct 16.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Study Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: September 16, 2005
• First Submitted That Met QC Criteria: September 16, 2005
• First Posted (Estimate): September 20, 2005

Study Record Updates

• Last Update Posted (Estimate): May 17, 2007
• Last Update Submitted That Met QC Criteria: May 16, 2007
• Last Verified: May 1, 2007

More Information

Terms related to this study

• Keywords: Reflex; Mitochondria; Altitude; Anoxemia; Genetic research
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Altitude Sickness
• Other Study ID Numbers: 2004-04