Document Detail


Elevated homocysteine, glutathione and cysteinylglycine concentrations in patients homozygous for the Chuvash polycythemia VHL mutation.
MedLine Citation:
PMID:  18223282     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In Chuvash polycythemia, homozygous von Hippel-Lindau (VHL) 598C>T leads to increased hypoxia inducible factor-1alpha and 2alpha, thromboses and lower systemic blood pressures. Circulating homocysteine, glutathione, gamma-glutamyltransferase and cysteinylglycine concentrations were higher in 34 VHL598C>T homozygotes than in 37 normal controls and cysteine was lower. Multivariate analysis showed elevated homocysteine independently associated with higher mean systemic blood pressures and elevated glutathione was associated with lower pressures to a similar degree. Among VHL598C>T homozygotes, homocysteine was elevated with low and normal folate concentrations, consistent with a possible defect in the remethylation pathway. The elevated glutathione and gamma-glutamyltransferase levels correlated positively with cysteinylglycine, consistent with possible upregulation of a glutathione synthetic enzyme and gamma-glutamyltransferase. Cysteinylglycine correlated inversely with cysteine, consistent with possible reduced cysteinyldipeptidase activity. We conclude that up-regulated hypoxia-sensing may influence multiple steps in thiol metabolism. The effects of the resultant elevated levels of homocysteine and glutathione on systemic blood pressure may largely balance each other out.
Authors:
Adelina I Sergueeva; Galina Y Miasnikova; Daniel J Okhotin; Alla A Levina; Zufan Debebe; Tatiana Ammosova; Xiaomei Niu; Elena A Romanova; Sergei Nekhai; Patricia M DiBello; Donald W Jacobsen; Josef T Prchal; Victor R Gordeuk
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-01-26
Journal Detail:
Title:  Haematologica     Volume:  93     ISSN:  1592-8721     ISO Abbreviation:  Haematologica     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-04     Completed Date:  2008-04-01     Revised Date:  2014-09-22    
Medline Journal Info:
Nlm Unique ID:  0417435     Medline TA:  Haematologica     Country:  Italy    
Other Details:
Languages:  eng     Pagination:  279-82     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Blood Pressure / genetics
Dipeptides / blood*
Female
Genetic Diseases, Inborn / blood*,  metabolism
Glutathione / blood*
Homocysteine / blood*
Homozygote*
Humans
Male
Point Mutation*
Polycythemia / blood*,  genetics
Von Hippel-Lindau Tumor Suppressor Protein / genetics*,  metabolism
gamma-Glutamyltransferase / metabolism
Grant Support
ID/Acronym/Agency:
5 R25-HL02679/HL/NHLBI NIH HHS; 5 RO1 HL079912-02/HL/NHLBI NIH HHS; MO1-RR10284/RR/NCRR NIH HHS; R01HL5007-13/HL/NHLBI NIH HHS; R01HL66333-01/HL/NHLBI NIH HHS; R37 HL052234/HL/NHLBI NIH HHS; R37 HL052234-14/HL/NHLBI NIH HHS; SC1 GM082325/GM/NIGMS NIH HHS; SC1 GM082325-01/GM/NIGMS NIH HHS; UH1-HL03679/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Dipeptides; 0LVT1QZ0BA/Homocysteine; 384644SZ9T/cysteinylglycine; EC 2.3.2.2/gamma-Glutamyltransferase; EC 6.3.2.19/Von Hippel-Lindau Tumor Suppressor Protein; GAN16C9B8O/Glutathione
Comments/Corrections

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