Research article

Abnormal energy regulation in early life: childhood gene expression may predict subsequent chronic mountain sickness

Luis Huicho^{* 1} , Guoqiang Xing^{* 2} , Clifford Qualls³ , María Rivera-Ch⁴ , Jorge L Gamboa⁵ , Ajay Verma⁶ and Otto Appenzeller⁷

¹Departament of Paediatrics, Universidad Nacional Mayor de San Marcos, Universidad Peruana Cayetano Heredia, and Instituto de Salud del Niño, Lima, Peru

²Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda MD, USA

³University of New Mexico, Department of Mathematics and Statistics and Clinical Research Center, University of New Mexico School of Medicine, Albuquerque NM 887131, USA

⁴Departament of Biological and Physiological Sciences, Faculty of Sciences and Philosophy, High Altitude Research Institute, Universidad Peruana Cayetano Heredia, Lima, Peru

⁵Department of Physiology, University of Kentucky, Lexington, Kentucky, USA

⁶Department of Neurology, Uniformed Services University of the Health Sciences, Bethesda MD, USA

⁷Department of Neurology, New Mexico Health Enhancement and Marathon Clinics Research Foundation, Albuquerque NM, USA

author email corresponding author email* Contributed equally

BMC Pediatrics 2008, 8:47doi:10.1186/1471-2431-8-47

Published:	27 October 2008

Abstract

Background

Life at altitude depends on adaptation to ambient hypoxia. In the Andes, susceptibility to chronic mountain sickness (CMS), a clinical condition that occurs to native highlanders or to sea level natives with prolonged residence at high altitude, remains poorly understood. We hypothesized that hypoxia-associated gene expression in children of men with CMS might identify markers that predict the development of CMS in adults. We assessed distinct patterns of gene expression of hypoxia-responsive genes in children of highland Andean men, with and without CMS.

Methods

We compared molecular signatures in children of highland (HA) men with CMS (n = 10), without CMS (n = 10) and in sea level (SL) children (n = 20). Haemoglobin, haematocrit, and oxygen saturation were measured. Gene expression in white cells was assessed at HA and then, in the same subjects, within one hour of arrival at sea level.

Results

HA children showed higher expression levels of genes regulated by HIF (hypoxia inducible factor) and lower levels of those involved in glycolysis and in the tricarboxilic acid (TCA) cycle. Pyruvate dehydrogenase kinase 1(PDK1) and HIF prolyl hydroxylase 3 (HPH3) mRNA expressions were lowest in children of CMS fathers at altitude. At sea level the pattern of gene expression in the 3 children's groups was indistinguishable.

Conclusion

The molecular signatures of children of CMS patients show impaired adaptation to hypoxia. At altitude children of CMS fathers had defective coupling between glycolysis and mitochondria TCA cycle, which may be a key mechanism/biomarker for adult CMS. Early biologic markers of disease susceptibility in Andeans might impact health services and social planning.