title: Elevated homocysteine, glutathione and cysteinylglycine concentrations in patients homozygous for the Chuvash polycythemia VHL mutation.
abstract: 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.affiliation: Cheboksary Children's Hospital, Cheboksary, Russia.
authors.forename: Adelina I
authors.initials: AI
authors.lastname: Sergueeva
authors.forename: Galina Y
authors.initials: GY
authors.lastname: Miasnikova
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Okhotin
authors.forename: Alla A
authors.initials: AA
authors.lastname: Levina
authors.forename: Zufan
authors.initials: Z
authors.lastname: Debebe
authors.forename: Tatiana
authors.initials: T
authors.lastname: Ammosova
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Niu
authors.forename: Elena A
authors.initials: EA
authors.lastname: Romanova
authors.forename: Sergei
authors.initials: S
authors.lastname: Nekhai
authors.forename: Patricia M
authors.initials: PM
authors.lastname: DiBello
authors.forename: Donald W
authors.initials: DW
authors.lastname: Jacobsen
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
authors.forename: Victor R
authors.initials: VR
authors.lastname: Gordeuk
mesh_terms: D001794:Blood Pressure / Q000235:genetics; D004151:Dipeptides / Q000097:blood*; D005260:Female; D030342:Genetic Diseases, Inborn / Q000097:blood* / Q000378:metabolism; D005978:Glutathione / Q000097:blood*; D006710:Homocysteine / Q000097:blood*; D006720:Homozygote; D006801:Humans; D008297:Male; D017354:Point Mutation; D011086:Polycythemia / Q000097:blood* / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics* / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D004151:Dipeptides; D006710:Homocysteine; C028505:cysteinylglycine; D005723:gamma-Glutamyltransferase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D005978:Glutathione