Linked Life Data

19481479

Source:http://linkedlifedata.com/resource/pubmed/id/19481479

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-10-19
pubmed:abstractText
Organismal response to hypoxia is essential for critical regulation of erythropoiesis, other physiological functions, and survival. There is evidence of individual variation in response to hypoxia as some but not all of the affected individuals develop polycythemia, and or pulmonary and cerebral edema. A significant population difference in response to hypoxia exist as many highland Tibetan, Ethiopian, and Andean natives developed adaptive mechanisms to extreme hypoxia. A proportion of non-adapted individuals exposed to high altitude develop pulmonary edema (HAPE), pulmonary hypertension, cerebral edema, and extreme polycythemia. The isolation of causative gene(s) responsible for HAPE and other extreme hypoxia complications would provide a rational basis for specific targeted therapy of HAPE, allow its targeted prevention for at-risk populations, and clarify the pathophysiology of other hypoxic maladaptations. The only suggested genetic linkage among unrelated individuals with HAPE has been with endothelial nitric oxide synthase (eNOS) gene. Here we describe a family with multiple members affected with HAPE in three generations. Families with multiple affected members with HAPE have not been described. We first ruled out linkage of HAPE with the eNOS gene. We then performed an analysis of the whole genome using high-density SNP arrays (Affymetrix v5.0) and, assuming a single gene causation of HAPE, ruled out linkage with 34 other candidate genes. Only the HIF2A haplotype was shared by individuals who exhibit the HAPE phenotype, and work on its possible causative role in HAPE is in progress. The small size of our family does not provide sufficient power for a conclusive analysis of linkage. We hope that collaboration with other investigators with access to more HAPE patients will lead to the identification of gene(s) responsible for HAPE and possibly other maladaptive hypoxic complications.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1096-0961
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
221-5
pubmed:dateRevised
2010-5-28
pubmed:meshHeading
pubmed-meshheading:19481479-Adaptation, Physiological, pubmed-meshheading:19481479-Altitude Sickness, pubmed-meshheading:19481479-Anaerobiosis, pubmed-meshheading:19481479-Asian Continental Ancestry Group, pubmed-meshheading:19481479-Basic Helix-Loop-Helix Transcription Factors, pubmed-meshheading:19481479-Female, pubmed-meshheading:19481479-Genome-Wide Association Study, pubmed-meshheading:19481479-Genotype, pubmed-meshheading:19481479-Haplotypes, pubmed-meshheading:19481479-Humans, pubmed-meshheading:19481479-Male, pubmed-meshheading:19481479-Microsatellite Repeats, pubmed-meshheading:19481479-Nitric Oxide Synthase Type III, pubmed-meshheading:19481479-Pedigree, pubmed-meshheading:19481479-Phenotype, pubmed-meshheading:19481479-Polymorphism, Single Nucleotide, pubmed-meshheading:19481479-Pulmonary Edema
pubmed:articleTitle
Genetic adaptation to extreme hypoxia: study of high-altitude pulmonary edema in a three-generation Han Chinese family.
pubmed:affiliation
Division of Hematology, School of Medicine, University of Utah, School of Medicine 5C210, 30 N 1900 E, Salt Lake City, Utah 84132, USA.
pubmed:publicationType
Journal Article, Retracted Publication, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural