Gene expression in the Andes; relevance to neurology at sea level.

Abstract

Chronic mountain sickness (CMS), a maladaptation syndrome to chronic hypoxia, occurs in the Andes. Gene expression differences in Andeans could explain adaptation and maladaptation to hypoxia, both of which are relevant to neurology at sea level. Expression of genes responsive to cellular oxygen concentration, hypoxia-inducible factor-1alpha (HIF-1alpha), three splicing variants of vascular endothelial growth factor (VEGF) and von Hippel-Lindau protein (pVHL) was measured by reverse transcription polymerase chain reaction (RT-PCR) in 12 Cerro de Pasco (CP) (altitude 4338 m) natives and 15 CMS patients in CP. Thirteen high altitude natives living in Lima and five Lima natives were sea level controls. A CMS score (CMS-sc) was assigned clinically. Expression was related to the clinical assessment. High expression of HIF-1alpha and VEGF-121 was found in CMS (P<0.001). Samples from CP had higher expression than those from Lima (P<0.001). Expression of HIF-1alpha and VEGF-121 was related to age (P<0.001); adjusting for age did not abolish the group effect. Higher CMS-sc was related to expression independent of age (P<0.001). VEGF-165 and -189 were expressed only in CMS. Birth altitude had no effect on gene expression. pVHL was not quantifiable.HIF-1alpha and VEGF-121 participate in adaptation to hypoxia. The high levels may explain blood vessel proliferation in Andeans and hold lessons for patients at sea level. VEGF-165 expression suggests that it contributes to preservation of neuronal function in human chronic hypoxia. VHL mutations may mark those destined to develop neural crest tumors which are common in the Andes.

• Authors: Otto Appenzeller, Tamara Minko, Vitaly Pozharov, Maurizio Bonfichi, Luca Malcovati, Jorge Gamboa, Luciano Bernardi
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 207 Issue 1-2 Pg. 37-41 (Mar 15 2003) ISSN: 0022-510X [Print] Netherlands
• PMID: 12614929 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA-Binding Proteins
• Endothelial Growth Factors
• HIF1A protein, human
• Hypoxia-Inducible Factor 1
• Hypoxia-Inducible Factor 1, alpha Subunit
• Intercellular Signaling Peptides and Proteins
• Lymphokines
• Nuclear Proteins
• Transcription Factors
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors

Topics

• Adult
• Altitude
• Altitude Sickness (genetics, metabolism, physiopathology)
• Analysis of Variance
• DNA-Binding Proteins (biosynthesis)
• Endothelial Growth Factors (biosynthesis)
• Gene Expression Regulation (physiology)
• Humans
• Hypoxia-Inducible Factor 1
• Hypoxia-Inducible Factor 1, alpha Subunit
• Intercellular Signaling Peptides and Proteins (biosynthesis)
• Lymphokines (biosynthesis)
• Male
• Middle Aged
• Nuclear Proteins (biosynthesis)
• Peru (epidemiology)
• Transcription Factors
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factors