Elevated levels of oxidized nucleosides in individuals with the JAK2V617F mutation from a general population study

It is unknown if the somatic mutations in chronic myeloproliferative neoplasms (MPNs), JAK2V617F and Calreticulin, are associated with oxidative stress, or impaired mitochondrial defense against reactive oxygen species. In the Danish General Suburban Population Study (GESUS), including 116 JAK2V617F...

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Published in:Redox biology 2021-05, Vol.41, p.101895-101895, Article 101895
Main Authors: Sørensen, Anders L., Hasselbalch, Hans C., Bjørn, Mads Emil, Nielsen, Claus H., Cordua, Sabrina, Skov, Vibe, Kjær, Lasse, Poulsen, Henrik E., Ellervik, Christina
Format: Article
Language:English
Subjects:
8-Hydroxy-2'-Deoxyguanosine
8-oxodG
8-oxoGuo
CALR
Calreticulin - genetics
Humans
JAK2V617F
Janus Kinase 2
Mutation
Myeloproliferative Disorders
Myeloproliferative neoplasms
Nucleosides
Oxidative stress
Oxidized nucleosides
Research Paper
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Summary:It is unknown if the somatic mutations in chronic myeloproliferative neoplasms (MPNs), JAK2V617F and Calreticulin, are associated with oxidative stress, or impaired mitochondrial defense against reactive oxygen species. In the Danish General Suburban Population Study (GESUS), including 116 JAK2V617F-mutated, 8 CALR-mutated, and 3310 mutation-negative participants without overt MPN, and in a study of 39 patients with myelofibrosis, the most advances type of MPNs, and 179 matched controls, we compared the urinary concentration of oxidized nucleosides – 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) – as markers of oxidative stress. In GESUS, we performed Mendelian randomization analyses, using the Ala16Val single nucleotide polymorphism in the superoxide dismutase2 (SOD2) gene. In the multivariate analyses in GESUS, the 8-oxodG and 8-oxoGuo concentration were 13% (95%CI: 6–21%, p 
ISSN:2213-2317
2213-2317
DOI:10.1016/j.redox.2021.101895