Document Detail


Uric acid: a danger signal from the RNA world that may have a role in the epidemic of obesity, metabolic syndrome, and cardiorenal disease: evolutionary considerations.
MedLine Citation:
PMID:  22000645     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
All human beings are uricase knockouts; we lost the uricase gene as a result of a mutation that occurred in the mid-Miocene epoch approximately 15 million years ago. The consequence of being a uricase knockout is that we have higher serum uric acid levels that are less regulatable and can be readily influenced by diet. This increases our risk for gout and kidney stones, but there is also increasing evidence that uric acid increases our risk for hypertension, kidney disease, obesity, and diabetes. This raises the question of why this mutation occurred. In this article we review current hypotheses. We suggest that uric acid is a danger and survival signal carried over from the RNA world. The mutation of uricase that occurred during the food shortage and global cooling that occurred in the Miocene epoch resulted in a survival advantage for early primates, particularly in Europe. Today, the loss of uricase functions as a thrifty gene, increasing our risk for obesity and cardiorenal disease.
Authors:
Richard J Johnson; Miguel A Lanaspa; Eric A Gaucher
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Seminars in nephrology     Volume:  31     ISSN:  1558-4488     ISO Abbreviation:  Semin. Nephrol.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-10-17     Completed Date:  2012-03-19     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  8110298     Medline TA:  Semin Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  394-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, Colorado 80045, USA. richard.johnson@ucdenver.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Evolution
Cardio-Renal Syndrome / epidemiology*,  genetics*
Humans
Metabolic Syndrome X / epidemiology*,  genetics*
Mutation
Obesity / epidemiology*,  genetics*
RNA*
Urate Oxidase / genetics
Uric Acid*
Grant Support
ID/Acronym/Agency:
HL-68607/HL/NHLBI NIH HHS; R01 HL068607-10/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
63231-63-0/RNA; 69-93-2/Uric Acid; EC 1.7.3.3/Urate Oxidase
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